Cancer
Critical Findings - Dietary Lycopene and Disease Risk

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: breast

Freudenheim JL

Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients.

Freudenheim JL, Marshall JR, Vena JE, Laughlin R, Brasure JR, Swanson MK, Nemoto T, Graham S.

J Natl Cancer Inst. 1996 Mar 20;88(6):340-8.

1996

BACKGROUND: Given the international variations in breast cancer incidence rates and the changes in breast cancer incidence amongmigrant populations, it has been hypothesized that diet is a factor influencing risk of this disease. Many studies indicate that a diet highin vegetables and fruits may protect against breast cancer.PURPOSE: We conducted a case-control study of diet, including the intake of non-food supplements, and premenopausal breast cancer risk. We evaluated in detail usual intake of vegetables and fruits (each measured as the total reported grams consumed for all queried vegetables and fruit), vitamins C and E, folic acid, individual carotenoids, and dietary fiber with its components. METHODS: Case patients (n=297) were identified through pathology records from hospitals in Erie and Niagara counties in western New York. They consisted of premenopausal women 40 years of age or oder who were diagnosed with breast cancer from November 1986 through April 1991. Control subjects (n=311), frequency-matched to case patients on the basis of age and county of residence, were randomly selected from New York State Department of Motor Vehicles records. In-person interviews included detailed reports of usual diet in the period 2 years before the interview. Unconditional logistic regression was used to estimate odds ratios (ORs)and 95% confidence intervals (CIs). RESULTS: There was a reduction in risk associated with high intake of several nutrients. With the lowest quartile of intake as the referent, adjusted ORs for the highest quartile of intake for specific nutrients were as follows: vitamin C (OR=0.53; 95% CI=0.33-0.86),-tocopheral (OR=0.55; 95% CI=0.34-0.88), folic acid (OR=0.50; 95% CI=0.31-0.82), -carotene (OR=0.67; 95% CI=0.42-1.08) and -carotene (OR=0.46;95% CI=0.28-0.74), lutein + zeaxanthin (OR=0.47; 95% CI=0.28.0-77), and dietary fiber from vegetables and fruits (OR=0.48; 95% CI=0.30-0.78). No association with risk was found for -cryptoxanthin, lycopene, or grain fiber. Fruits were weakly associated with a reduction in risk (4th quartile OR=0.67; 95% CI=0.42-1.09). No association was found between breast cancer risk and intake of vitamins C and E and folic acid taken as supplements. A strong inverse association between total vegetable intake and risk was observed (4th quartile OR=0.46; 95% CI=0.28-0.74). This inverse association was found to be independent of vitamin C,-tocopherol, folic acid, dietary fiber, and -carotene. Adjusting for -carotene or lutein + zeaxanthin somewhat attenuated the inverse association with vegetable intake. CONCLUSIONS: In this population, intake of vegetables appears to decrease premenopausal breast cancer risk. This effect may be related in part, to -carotene and lutein + zeaxanthin in vegetables. It appears, however, that, of the nutrients and food components examined, no single dietary factor explains the effect. Evaluated components found together in vegetables may have a synergistic effect on breast cancer risk; alternatively, other unmeasured factors in these foods may also influence risk.

(-)
veg

Cancer: breast

Zhang S

Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects.

Zhang S, Tang G, Russell RM, Mayzel KA, Stampfer MJ, Willett WC, Hunter DJ.

Am J Clin Nutr. 1997 Sep;66(3):626-32.

1997

A case-control study of the associations of retinoids and specific carotenoids with breast cancer using concentrations of these nutrients in breast adipose tissue was conducted among women attending a breast clinic in the Boston area in 1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n = 46) were women whose biopsies revealed invasive or in situ breast cancer; control subjects (n = 63) were women whose biopsies revealed benign disease. We observed inverse associations between breast adipose concentrations of retinoids and carotenoids and risk of breast cancer, although not all were statistically significant. The multivariate-adjusted odds ratio comparing women above the median value of the control group for retinol with those below or equal to the median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61 (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for beta-carotene, 0.32 (95% CI: 0.11, 0.94) for ycopene, and 0.68 (95% CI: 0.27, 1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and dietary intake of preformed vitamin A, including supplements measured by using a food-frequency questionnaire. No correlation was found between breast adipose concentrations of carotenoids and intake of dietary carotenoids. These data suggest that higher breast adipose concentrations of retinoids and some carotenoids may be associated with decreased risk of breast cancer and that further examination of these relations is warranted.

(-)

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: breast

Ronco A

Vegetables, fruits, and related nutrients and risk of breast cancer: a case-control study in Uruguay.

Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Leborgne F.

Nutr Cancer. 1999;35(2):111-9.

1999

To evaluate whether the protective effect associated with vegetables and fruits in breast cancer could be explained by nutrients and bioactive substances present in these plant foods, we carried out a case-control study in Uruguay including 400 cases and 405 controls. The intake of vegetables, fruits, and related nutrients was estimated with a food frequency questionnaire on 64 food items. This questionnaire allowed the calculation of total energy intake, and nutrients were calorie adjusted by the residuals method. Odds ratios for study variables were estimated by unconditional multiple logistic regression. Total vegetable, total fruit, dietary fiber, vitamin C, vitamin E, lycopene, folate, and total phytosterol intakes were inversely associated with breast cancer risk [4th quartile odds ratio for total vegetable intake = 0.41, 95% confidence interval = 0.26-0.65, p (for trend) = 0.004]. The association with total vegetable intake was not independent of lycopene intake. The results related to vegetable and nutrient intakes are consistent with antioxidant and antiestrogenic effects. This could be mediated, among other nutrients, by dietary fiber and lycopene intake. The role of other unmeasured phytochemicals, correlated with dietary fiber and lycopene intakes, cannot be ruled out.

(-)

Cancer: breast

Levi F

Dietary intake of selected micronutrients and breast-cancer risk.

Levi F, Pasche C, Lucchini F, La Vecchia C.

Int J Cancer. 2001 Jan 15;91(2):260-3.

2001

The relation between 17 micronutrients and breast-cancer risk was analyzed in a case-control study conducted between 1993 and 1999 in the Swiss Canton of Vaud. Cases were 289 women with incident, histologically confirmed breast cancer, and controls were 442 women admitted to the same hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratios (ORs) were obtained after allowance for age, education, parity, menopausal status, body mass index, total energy intake and alcohol drinking. For several micronutrients, the ORs tended to decline with increasing tertile of intake, with significant inverse trends in risk for potassium (OR for the highest tertile = 0.21), total carotenoids (OR = 0.42), lycopene (OR = 0.43), folic acid (OR = 0.45), vitamin C (OR = 0.19), vitamin E (OR = 0.37) and vitamin B(6) (OR = 0.54). In a model including a continuous term for the 7 micronutrients significantly related to breast cancer, the only persisting significant inverse relations were for vitamin C (OR = 0.23) and lycopene (OR = 0.64).

(-)

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: breast

La Vecchia C

Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms.

La Vecchia C

Exp Biol Med (Maywood). 2002 Nov;227(10):860-3.

2002

Tomato consumption showed a consistent inverse relation with the risk of digestive tract neoplasms in Italy in an integrated series of studies conducted in the 1980s. Another series of case-control studies was conducted between 1992 and 1999 in different areas of Italy. Cases were patients below age 80 with incident, histologically confirmed cancer of the oral cavity and pharynx (n = 754), esophagus (n = 304), colorectum (n = 1953), breast (n = 2529), and ovary (n = 1031). The comparison group involved, overall, over 5000 patients below age 80 with acute, non-neoplastic, nonhormone-related diseases, unrelated to long-term diet modifications and admitted to the same network of hospitals. Information was collected in hospital by trained interviewers using a validated food frequency questionnaire, including 78 foods or groups of foods, various alcoholic beverage, and fat-intake pattern. The multivariate relative risk (RR) of oral, pharyngeal, and esophageal cancer decreased across subsequent levels of lycopene intake to reach 0.7 (95% confidence interval [CI] 0.4-1.0) for oral and pharyngeal, and 0.7 (95% CI 0.4-1.1) for esophageal cancer in the highest quintile of intake. Both trends in risk were of borderline statistical significance. With reference to colorectal, breast, and ovarian cancer, although no consistent association was observed for lycopene (RR = 1.0 for colorectal, 1.2 for breast, and 1.1 for ovary in the highest quintile), tomato intake was inversely and significantly related with colorectal cancer (RR = 0.8). The inverse relation between lycopene and upper digestive tract neoplasms was not explained by alcohol or tobacco, sociodemographic factors, or total energy intake. The interpretation of such an inverse relation, however, remains open to discussion because it may be related to an effect of lycopene due to its antioxidant effect and/or a potential role of lycopene in decreasing insulin growth factor I, which is a promoter in the process of carcinogenesis.

Cancer: breast

Huang JP

Dietary carotenoids and risk of breast cancer in Chinese women.

Huang JP, Zhang M, Holman CD, Xie X.

Asia Pac J Clin Nutr. 2007;16 Suppl 1:437-42.

2007

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, the protective effect of carotenoids on breast cancer has been inconclusive. To investigate whether intake of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin is inversely associated with breast cancer risk, a case-control study was conducted in China during 2004-2005. The cases were 122 female patients aged 24-87 years with histopathologically confirmed breast cancer. 632 healthy women age-matched were randomly recruited from outpatient clinics. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable food frequency questionnaire. The USDA nutrient composition database was used to calculate intake of the specific carotenoids. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), accounting for age, locality, education, body mass index, smoking, passive smoking, physical activity, number of children breastfed, menopausal status, oral contraceptive use, biopsy-confirmed benign breast diseases, family history of breast cancer, and total energy intake. Compared with the highest versus lowest quartile of intake, the adjusted ORs were 0.26 (95% CI 0.14-0.46) for lycopene, 0.38 (95% CI 0.21-0.71) for beta-carotene, 0.43 (95% CI 0.23-0.82) for beta-cryptoxanthin, and 0.37 (95% CI 0.20-0.68) for total carotenoids, with statistically significant tests for trend. There was no association with breast cancer for alpha-carotene and lutein/zeaxanthin. It is concluded that higher intake of lycopene, beta-carotene and beta-cryptoxanthin is associated to a lower risk of breast cancer among Chinese women. More research to examine the relationship between carotenoids and breast cancer risk is warranted.

(-)
↓

risk

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: breast

Wang C

No evidence of association between breast cancer risk and dietary carotenoids, retinols, vitamin C and tocopherols in Southwestern Hispanic and non-Hispanic White women.

Wang C, Baumgartner RN, Yang D, Slattery ML, Murtaugh MA, Byers T, Hines LM, Giuliano AR, Baumgartner KB.

Breast Cancer Res Treat. 2009 Mar;114(1):137-45. Epub 2008 Aug 1.

2009

OBJECTIVES: The effects of dietary intake of antioxidant vitamins on breast cancer risk are inconclusive. Moreover, little is known as to whether associations differ between non-Hispanic White (NHW) and Hispanic women. We assessed the associations of the dietary intake of antioxidant vitamins commonly found in fruits and vegetables with breast cancer risk and estrogen receptor (ER) status among NHW and Hispanic women living in the Southwestern U.S. MATERIALS AND METHODS: Primary breast cancer cases in the 4-Corners region (Arizona, Colorado, New Mexico, Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls were frequency matched by ethnicity and age (+/-5 years). Information on demographic characteristics and other breast cancer risk factors prior to the referent year were collected by interviewer-administered computerized questionnaire. A modified extensive diet history questionnaire was used to assess dietary intake. RESULTS: We did not find a protective effect of dietary antioxidants, such as alpha or beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, lycopene, retinol, vitamin C, alpha, delta, beta or gamma-tocopherol, on breast cancer risk in populations living in the Southwest. We did not find any consistent associations with multivariate risk of breast cancer or estrogen receptor status. Cigarette smoking was not a significant effect modifier of these associations. CONCLUSION: This case-control study did not find any meaningful association of the dietary intake of antioxidant vitamins with breast cancer risk or ER status.

Cancer: breast

Terry P

Dietary carotenoids and risk of breast cancer.

Terry P, Jain M, Miller AB, Howe GR, Rohan TE.

Am J Clin Nutr. 2002 Oct;76(4):883-8.

2002

BACKGROUND: Many studies of fruit and vegetable consumption showed inverse associations with breast cancer risk, suggesting the potential importance of carotenoids (and other phytochemicals) contained in these foods. To date, however, only one prospective cohort study has examined dietary carotenoids other than beta-carotene in relation to breast cancer risk. OBJECTIVE: Our aim was to examine the relations between dietary intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, and lutein + zeaxanthin and breast cancer risk in a large cohort study of Canadian women. DESIGN: A case-cohort analysis was undertaken in a cohort of 56 837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993 a total of 1589 women were diagnosed with biopsy-confirmed incident breast cancer. For comparison, a subcohort of 5681 women was randomly selected. After exclusions for various reasons, the analyses were based on 1452 cases and 5239 noncases. RESULTS: We found no clear association between intakes of any of the studied carotenoids and breast cancer risk in the study population as a whole or in subgroups defined by smoking status; relative body weight (assessed by body mass index); intakes of total fat, energy, alcohol, or folic acid; family history of breast cancer; or menopausal status. CONCLUSIONS: Our data do not support any association between dietary intakes of the studied carotenoids and breast cancer risk. However, prospective cohort studies of carotenoids in relation to breast cancer are scarce and further studies are warranted.

CC
nested

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: breast

Jarvinen R

Diet and breast cancer risk in a cohort of Finnish women.

Jarvinen R, Knekt P, Seppanen R, Teppo L.

Cancer Lett. 1997 Mar 19;114(1-2):251-3.

1997

The associations between dietary antioxidant vitamins, dietary fiber, and selected foods and risk of breast cancer were studied in 4697 initially cancer-free women, aged 15 years or older. At baseline (1967-1972) the women were interviewed for total habitual diet over the preceding year. During a 25-year follow-up period 88 breast cancer cases were diagnosed. There was a significant inverse gradient between milk consumption and occurrence of breast cancer, whereas higher consumption of fried meat was associated with increased risk of breast cancer. No significant relationships were found between the intakes of vitamin E, vitamin C, beta-carotene, lycopene, lutein or dietary fiber and the occurrence of breast cancer.

Cancer: breast

Cui Y

Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study.

Cui Y, Shikany JM, Liu S, Shagufta Y, Rohan TE.

Am J Clin Nutr. 2008 Apr;87(4):1009-18.

2008

BACKGROUND: Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status. OBJECTIVE: We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women. DESIGN: Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest. RESULTS: Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall. CONCLUSION: Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.

N

may
↓
risk

if have ER (+) PR predisposi tion

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: cervical

VanEenwyk J

Dietary and serum carotenoids and cervical intraepithelial neoplasia.

VanEenwyk J, Davis FG, Bowen PE.

Int J Cancer. 1991 Apr 22;48(1):34-8.

1991

A case-control study examined the association between cervical intra-epithelial neoplasia (CIN) and serum and dietary alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene. Cases (n = 102) had biopsy confirmed CIN I, II or III. Controls matched for age, ethnic origin and clinic (n = 102) had normal Pap smears. Participants completed health history and food frequency questionnaires. Fasting venous blood samples were assayed for serum carotenoids. Multivariable conditional logistic regression analyses yielded odds ratios and 95% confidence intervals (CIs) for those in quartiles 3, 2, and 1 (lowest) compared to quartile 4 (highest) of serum lycopene of 3.5 (1.1-11.5), 4.7 (1.2-17.7) and 3.8 (1.1-12.4), respectively. Similar analyses yielded adjusted odds ratios (ORaS) and 95% CIs of 4.6 (1.1-19.7), 5.8 (1.6-21.3) and 5.4 (1.3-23.3) for dietary intake of lycopene. The findings for lycopene-rich foods (tomatoes) were consistent with this result. CIN was not associated with the lutein. Findings for alpha-carotene, beta-carotene and cryptoxanthin were ambiguous. Quartile of vitamin C intake was also inversely associated with CIN with ORaS and 95% CIs of 3.7 (0.9-14.6), 4.1 (1.0-17.2), and 6.4 (1.4-30.0) for those in quartiles 3, 2, and 1 compared to quartile 4.

(-)

Cancer: cervical

Kanetsky PA

Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-Hispanic, black women.

Kanetsky PA, Gammon MD, Mandelblatt J, Zhang ZF, Ramsey E, Dnistrian A, Norkus EP, Wright TC Jr.

Nutr Cancer. 1998;31(1):31-40.

1998

We examined whether elevated levels of retinoids, carotenoids, folate, and vitamin E protected against cervical dysplasia among non-Hispanic, black women. We enrolled 32 women with incident cervical dysplasia, including cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III/carcinoma in situ, and 113 control women with normal cervical cytology in case-control study. Micronutrient levels were estimated from a food-frequency questionnaire (FFQ) and measured from blood samples. Information on risk factors for cervical neoplasia was elicited by interview. Hybrid capture was used to determine infection with human papillomavirus. After adjustment for potential confounders, analysis of micronutrient levels estimated from the FFQ suggested that women in the upper tertile of lycopene and vitamin A intake were one-third (odds ratio = 0.32, 95% confidence interval = 0.8-1.3) and one-fourth (odds ratio = 0.24, 95% confidence interval = 0.05-1.2) as likely, respectively, to have dysplasia as women in the lower tertile. Borderline protective trends (p < or = 0.10) were apparent. Elevated levels of serum lycopene also suggested some protection against dysplasia. Results were not significant at alpha = 0.05 because of the small number of case women enrolled. Overall, correlations between estimates from the FFQ and serum levels were poor. This study indicates that, among black women, lycopene and perhaps vitamin A may play a protective role in the early stages of cervical carcinogenesis.

(-) p=0.1

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: colorectal

Enger SM

Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas.

Enger SM, Longnecker MP, Chen MJ, Harper JM, Lee ER, Frankl HD, Haile RW.

Cancer Epidemiol Biomarkers Prev. 1996 Mar;5(3):147-53.

1996

We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

Cancer: colorectal

Levi F

Selected micronutrients and colorectal cancer. a case-control study from the canton of Vaud, Switzerland.

Levi F, Pasche C, Lucchini F, La Vecchia C.

Eur J Cancer. 2000 Oct;36(16):2115-9.

2000

The association between dietary intake of various micronutrients and colorectal cancer risk was analysed using data from a case-control study conducted between 1992 and 1997 in the Swiss Canton of Vaud. Cases were 223 subjects (142 (64%) males, 81 (36%) females; median age 63 years) with incident, histologically confirmed colon (n=119; 53%) or rectal (n=104; 47%) cancer, and controls were 491 subjects (211 (43%) males, 280 (57%) females; median age 58 years; range 27-74) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions, unrelated to long-term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire (FFQ). Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity, and total energy and fibre intake. No significant association was observed for calcium, retinol, folate, vitamin D or E. The risk of colorectal cancer was directly associated with measures of iron intake (OR=2.43 for the highest tertile, 95% confidence interval (CI): 1.2-5.1) and inversely associated with vitamin C (OR=0.45; 95% CI: 0.3-0.8), and non-significantly with total carotenoids (OR=0.66, 95% CI: 0.4-1.1). Among various individual carotenoids considered, inverse associations were observed for alpha-carotene, beta-carotene and lutein/zeaxanthin. These findings were consistent across the strata of gender and age, and support the hypothesis that selected micronutrients have a favourable effect on colorectal carcinogenesis.

N

total

carotonoids

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: colorectal

Slattery M. L.

Carotenoids and colon cancer.

Slattery ML, Benson J, Curtin K, Ma KN, Schaeffer D, Potter JD.

Am J Clin Nutr. 2000 Feb;71(2):575-82.

2000

BACKGROUND: Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. OBJECTIVE: The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. DESIGN: Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). RESULTS: Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P < 0.01 for linear trend). The associations with other carotenoids were unremarkable. CONCLUSION: The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

(-)

lutein

Cancer: colorectal

La Vecchia C

Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms

La Vecchia C

Exp Biol Med (Maywood). 2002 Nov;227(10):860-3.

2002

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: colorectal

Nkondjock A

Dietary carotenoids and risk of colon cancer: case-control study.

Nkondjock A, Ghadirian P.

Int J Cancer. 2004 May 20;110(1):110-6.

2004

Some epidemiological studies suggest that consumption of fruits and vegetables with a high carotenoid content may protect against colon cancer (CC). The evidence, however, is not completely consistent. Given the inconsistencies in findings in previous studies and continued interest in identifying modifiable risk factors for CC, a case-control study of French-Canadian in Montreal, Canada, was undertaken to examine the possible association between dietary carotenoids and CC risk and to investigate whether this association varies in relation to lifestyle factors such as smoking or diet, and particularly the high consumption of long-chain polyunsaturated fatty acids (LCPUFA). A total of 402 colorectal cases (200 males and 202 females) and 688 population-based controls matched for age, gender and place of residence were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on over 200 food items and recipes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in unconditional logistic regression models. After adjustment for important variables such as total energy intake, no association was found between dietary intake of carotenoids and CC risk. For women with high intakes of LCPUFA, an inverse association was found between lutein + zeaxanthin and CC risk. ORs were 0.41; 95%CI (0.19-0.91), p=0.03 for eicosapentaenoic acid, and OR=0.36, 95%CI (0.19-0.78), p=0.01 for docosahexaenoic acid, when the upper quartiles of intake were compared to the lower. Among never-smokers, a significantly reduced risk of CC was associated with intake of beta-carotene [OR=0.44, 95%CI (0.21-0.92) and p=0.02], whereas an inverse association was found between lycopene intake and CC risk [OR=0.63, 95%CI (0.40-0.98) and p=0.05] among smokers. The results of our study suggest that a diet rich in both lutein + zeaxanthin and LCPUFAs may help prevent CC in French-Canadian females.

(-)
↓
risk in
smokers

Cancer: colorectal

Kune G

Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene.

Kune G, Watson L.

Nutr Cancer. 2006;56(1):11-21.

2006

The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: colorectal

Slattery ML

Tumor markers and rectal cancer: support for an inflammation-related pathway.

Slattery ML, Wolff RK, Herrick J, Caan BJ, Samowitz W.

Int J Cancer. 2009 Oct 1;125(7):1698-704.

2009

Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases withinterview and tumor DNA were compared to 1,205 population-based controls. Study participants were from Utah and the Northern California Kaiser Permanente Medical Care Program. Tumor DNA was analyzed for TP53 and KRAS2 mutations and CpG Island methylator phenotype. We assessed how these tumor markers were associated with use of anti-inflammatory drugs, polymorphisms in the IL6 genes (rs1800795 and rs1800796) and dietary antioxidants. Ibuprofen-type drugs, IL6 polymorphisms (rs1800796) and dietary alpha-tocopherol and lycopene significantly altered likelihood of having a TP53 mutation. This was especially true for TP53 transversion mutations and dietary antioxidants (OR for beta-carotene 0.51 95% CI 0.27, 0.97, p trend 0.03; alpha-tocopherol 0.41 95% CI 0.20, 0.84, p trend 0.02) Beta-carotene and ibuprofen significantly altered risk of KRAS2 tumors. The associations between lutein and tocopherol and TP53 and KRAS2 mutations were modified by IL6 genotype. These results suggest that inflammation-related factors may have unique associations with various rectal tumor markers. Many factors involved in an inflammation-related pathway were associated with TP53 mutations and some dietary factors appeared to be modified by IL6 genotype.

(-)

↓

likelihood of TP53 mutation

Cancer: colorectal

Terry P

Dietary carotenoid intake and colorectal cancer risk.

Terry P, Jain M, Miller AB, Howe GR, Rohan TE.

Nutr Cancer. 2002;42(2):167-72.

2002

Several studies have found inverse associations between fruit and vegetable consumption and colorectal cancer risk, suggesting the potential etiological importance of carotenoids (and other phytochemicals) contained in these foods. However, only one study (a case-control study) has examined the association between dietary carotenoids other than beta-carotene and colorectal cancer risk. In the study reported here, we examined the relationships between dietary intakes of beta-carotene, alpha-carotene, lycopene, lutein, and beta-cryptoxanthin and colorectal cancer risk in a large cohort study of Canadian women. A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993, a total of 388 women were diagnosed with colorectal cancer. For comparative purposes, a subcohort of 5,681 women was randomly selected. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 noncases. We did not find any clear association between intake of any of the studied carotenoids and colorectal cancer risk in the study population as a whole or in subgroups defined by smoking status, relative body weight (body mass index), intakes of total fat, energy, alcohol, and folic acid, or menopausal status. Our data do not support any association between dietary intakes of the studied carotenoids and colorectal cancer risk. However, given that this is the first prospective cohort study of carotenoids in relation to colorectal cancer, further studies are warranted.

CC nested

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: colorectal

Mannisto S

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies.

Mannisto S, Yaun SS, Hunter DJ, Spiegelman D, Adami HO, Albanes D, van den Brandt PA, Buring JE, Cerhan JR, Colditz GA, Freudenheim JL, Fuchs CS, Giovannucci E, Goldbohm RA, Harnack L, Leitzmann M, McCullough ML, Miller AB, Rohan TE, Schatzkin A, Virtamo J, Willett WC, Wolk A, Zhang SM, Smith-Warner SA.

Am J Epidemiol. 2007 Feb 1;165(3):246-55. Epub 2006 Dec 11.

2007

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.

Meta

11 PC
N
Amer & Europe

Cancer: colorectal

Malila N

Dietary and serum alphatocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers.

Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L.

Eur J Clin Nutr. 2002 Jul;56(7):615-21.

2002

OBJECTIVE: To study the association between dietary and serum antioxidant vitamins and carotenoids and risk for colorectal cancer in male smokers. DESIGN: A prospective cohort study within a randomised, double-blind, placebo-controlled trial testing supplementation with alpha-tocopherol (50 mg/day), beta-carotene (20 mg/day) or both in preventing cancer. SUBJECTS AND METHODS: Participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study with complete dietary data and serum samples available from baseline. These included 26,951 middle-aged male smokers among whom 184 colorectal cancer cases were diagnosed during 8 y of follow-up. Relative risks were calculated with Cox proportional hazards models adjusting for trial supplementation, age, body mass index, serum cholesterol, cigarettes smoked per day and physical activity. RESULTS: There was no significant association between dietary vitamin C or E, alpha-or gamma-tocopherol, retinol, alpha- or beta-carotene, lycopene or lutein+zeaxanthin and risk for colorectal cancer. Serum alpha-tocopherol, beta-carotene or retinol was also not associated with the risk, neither did the season when baseline blood was drawn modify the relationship between serum beta-carotene and colorectal cancer risk. CONCLUSIONS: Our data support the results from previous studies in which no association between dietary antioxidant vitamins and carotenoids and risk for colorectal cancer has been observed. Likewise, no association between baseline serum antioxidant concentrations and colorectal cancer risk was evident. SPONSORSHIP: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by a contract with the US National Cancer Institute (N01-CN-45165).

Disease
type

First
Author

Study Title
and Complete Citation

Date

Abstract

Study
Type

G.Tom
+, N,

P.Tom
+, N,

F.Tom
+, N, -

Lyco
+, N,

Other
+, N,

Cancer: colorectal

Park SY

Carotenoid intake and colorectal cancer risk: the multiethnic cohort study.

Park SY, Nomura AM, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN.

J Epidemiol. 2009;19(2):63-71. Epub 2009 Mar 6.

2009

BACKGROUND: A protective effect of fruits and vegetables against colorectal cancer has been supported by many epidemiologic studies. This suggests that the carotenoids frequently found in these foods play a role in the prevention of this common cancer. To examine associations between the intake of individual and total carotenoids and the risk of colorectal cancer, we analyzed prospective data from the Multiethnic Cohort Study. METHODS: This analysis includes 85 898 men and 105 106 women who completed a quantitative food frequency questionnaire in 1993-1996. The participants were African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites aged 45-75 years at cohort entry. After an average follow-up of 8.2 years, 1292 and 1086 incident cases of colorectal cancer were identified in men and women, respectively. Cox proportional hazard models were used to estimate relative risks of colorectal cancer. RESULTS: No significant associations were found between intake of individual and total carotenoids and colorectal cancer risk either in men or women, except for beta-cryptoxanthin, which showed a mild protective effect in men. When the associations were investigated separately for colon and rectal cancer, lycopene intake was related to an increased risk of rectal cancer in men. A decreased risk was seen for total beta-carotene in male current smokers, but the test for interaction with smoking status was not significant. No association was observed in each ethnic-sex group. CONCLUSION: Overall, our findings do not support a significant association between carotenoid intake and colorectal cancer, although some associations were seen in subgroup analyses.

(+)

↑
rectal
cancer risk in men

Cancer: endnometerial

Jain MG

Nutritional factors and endometrial cancer in Ontario, Canada.

Jain MG, Howe GR, Rohan TE.

Cancer Control. 2000 May-Jun;7(3):288-96.

2000

No abstract available. Paper was reviewed. The first few paragraphs follow: Despite recent declines in the incidence rate, endometrial cancer remains a major cause of morbidity among women. Most risk factors pertain to reproductive factors and hormone replacement therapy that affect a woman’s hormonal milieu. There is also a strong association between endometrial cancer and obesity. The fact that diet is associated with both serum hormone levels 5 and obesity— the two important risk factors for endometrial cancer — makes the effect of diet on endometrial cancer particularly relevant. Most of the epidemiologic data pertaining to the relationship between diet and endometrial cancer derive from ecologic and case-control studies. The ecologic studies routinely implicate fat as a risk factor, yet these studies are unable to establish whether the observed effect is independent f obesity or other known risk factors for endometrial cancer. While there are some reports of elevated risks with consumption of animal fat and decreased risk with carotene intakes, these are not consistently supported by case-control studies and also are not supported by the only cohort study on diet and endometrial cancer reported to date. The present study was conducted to assess the role of various nutritional factors and obesity on the risk of developing endometrial cancer in Ontario, Canada.

Disease
type

First
Author

Study Title
and Complete Citation

Date

Abstract

Study
Type

G.Tom
+, N,

P.Tom
+, N,

F.Tom
+, N, -

Lyco
+, N,

Other
+, N,

Cancer: endnometerial

Jain MG

A cohort study of nutritional factors and endometrial cancer.

Jain MG, Rohan TE, Howe GR, Miller AB.

Eur J Epidemiol. 2000;16(10):899-905.

2000

To evaluate the role of nutritional factors in the etiology of endometrial cancer, we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a subcohort was constructed by selecting a 10% random sample from the 56,837 women in the dietary cohort. Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31, 1993 and ascertained by record linkage to the Canadian Cancer Database. Information on usual diet at enrollment and other epidemiological variables was collected by means of self-administered questionnaires. Hazard ratios were obtained from proportional hazards regression models, with estimation of robust standard errors. We found a strong association of endometrial cancer with body mass index > 25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06-3.50). Endometrial cancer risk was not associated significantly with intakes of total energy, carbohydrates, proteins, total fat and major fatty acids, total dietary fiber and various types of fibers, vitamin C, E and A, folic acid, beta-carotene, lutein, or cryptoxanthin. Some decrease in risk was noted with relatively high intakes of saturated fat, animal fat or lycopene. The associations observed in the study were independent of total energy intake and most non-dietary risk factors. The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women.

Cancer: endometri al

Pelucchi C

Dietary intake of carotenoids and retinol and endometrial cancer risk in an Italian case-control study.

Pelucchi C, Dal Maso L, Montella M, Parpinel M, Negri E, Talamini R, Giudice A, Franceschi S, La Vecchia C.

Cancer Causes Control. 2008 Dec;19(10):120915. Epub 2008 Jul 1.

2008

OBJECTIVES: To provide information on the relation between intake of carotenoids and retinol and endometrial cancer, since available data are inconsistent. Further, carotenoids other than beta-carotene have been rarely investigated. METHODS: We conducted a multi-centric case-control study in various areas of Italy between 1992 and 2006 on 454 women with incident, histologically confirmed endometrial cancer and 908 controls admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. Intake of carotenoids and retinol was computed from a validated and reproducible food frequency questionnaire. We adjusted for selected covariates, including energy intake, and calculated multivariate odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression. RESULTS: Comparing the highest to the lowest quartile of intake, the ORs of endometrial cancer were 0.69 (95% CI, 0.48-0.99) for beta-carotene, 0.65 (95% CI, 0.45-0.94) for beta-cryptoxanthin, and 0.59 (95% CI, 0.41-0.85) for lutein plus zeaxanthin intake. No association emerged with retinol (OR = 1.31, 95% CI, 0.94-1.84), alpha-carotene (OR = 0.94, 95% CI, 0.66-1.34), and lycopene (OR = 0.95, 95% CI, 0.68-1.34). CONCLUSIONS: Our results support a favorable role of selected dietary carotenoids on endometrial cancer risk.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: endometrial

McCann SE

Diet in the epidemiology of endometrial cancer in western New York (United States).

McCann SE, Freudenheim JL, Marshall JR, Brasure JR, Swanson MK, Graham S.

Cancer Causes Control. 2000 Dec;11(10):965-74.

2000

OBJECTIVES: We examined diet and risk of endometrial cancer among women in the Western New York Diet Study (1986-1991). METHODS: Self-reported frequency of use of 172 foods and beverages during the 2 years before the interview and other relevant data were collected by detailed interviews from 232 endometrial cancer cases and 639 controls, frequency-matched for age and county of residence. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education, body mass index (BMI), smoking history, hypertension, diabetes, age at menarche, parity, oral contraceptive use, menopausal status, menopausal estrogen use, and energy. RESULTS: Risks were reduced for women in the highest quartiles of intake of protein (OR 0.4, 95% CI: 0.2-0.9), dietary fiber (OR 0.5, 95% CI: 0.3-1.0), phytosterols (OR 0.6, 95% CI: 0.3-1.0), vitamin C (OR 0.5, 95% CI: 0.3-0.8) folate (OR 0.4, 95% CI: 0.2-0.7), alpha-carotene (OR 0.6, 95% CI: 0.4-1.0), beta-carotene (OR 0.4, 95% CI: 0.2-0.6), lycopene (OR 0.6, 95% CI: 0.4-1.0), lutein + zeaxanthin (OR 0.3, 95% CI: 0.2-0.5) and vegetables (OR 0.5, 95% CI: 0.3-0.9), but unrelated to energy (OR 0.9, 95% CI: 0.6-1.5) or fat (OR 1.6, 95% CI: 0.7-3.4). CONCLUSIONS: Our results support previous findings of reduced endometrial cancer risks associated with a diet high in plant foods.

(-)

margianl
↓

risk for endo cancer

V (-)

Lutein
(-)

Cancer: gastric

Garcia-Closas R

Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain.

Garcia-Closas R, Gonzalez CA, Agudo A, Riboli E. Cancer

Causes Control. 1999 Feb;10(1):71-5.

1999

OBJECTIVES: To investigate the relationship between gastric cancer and the intake of specific carotenoids (alpha-carotene, beta-carotene, lutein, and lycopene) and flavonoids (quercetin, kaempferol, myricetin, and luteolin) using new data on their concentration in foods. METHODS: Case-control study carried out in Spain that included 354 cases of gastric cancer and 354 controls, matched by age, gender, area of residence and hospital. Usual food intake was assessed using a dietary history questionnaire. RESULTS: In a multivariate model adjusted for several dietary factors, no association was found between intake of any of the studied carotenoids and the risk of gastric cancer. The adjusted OR of gastric cancer for the highest quartile of total flavonoid intake versus the lowest quartile was 0.44 (95 percent confidence interval [CI] = 0.25-0.78; P for trend = 0.003). Kaempferol intake was found to be protective (OR = 0.48; CI = 0.26-0.88; P for trend = 0.04) comparing the highest versus the lowest quartile of intake. A trend toward lower risk of stomach cancer with higher intake of quercetin was also found. CONCLUSIONS: The results of this study support the hypothesis that the well-established protective effect of fruit and vegetables against gastric cancer could, in part, be due to the presence of flavonoids.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: gastric

De Stefani E

Vegetables, fruits, related dietary antioxidants, and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay.

De Stefani E, Brennan P, Boffetta P, Ronco AL, Mendilaharsu M, Deneo-Pellegrini H.

Nutr Cancer. 2000;38(1):23-9.

2000

In 1998-1999, a case-control study on esophageal cancer was conducted in Uruguay. For this purpose, 111 cases with squamous cell carcinoma of the esophagus and 444 controls with conditions unrelated to tobacco smoking, alcohol drinking, or recent changes in the diet were frequency matched on age, gender, residence, and urban/rural status. Vegetables and, more markedly, fruits were associated with strong reductions in risk. On the other hand, 12 of 15 dietary antioxidants displayed significant inverse associations with esophageal cancer risk. The strongest effect was observed for high intake of beta-cryptoxanthin (odds ratio = 0.16, 95% confidence interval = 0.08-0.36). Also, alpha-carotene, lycopene, and beta-sitosterol were associated with significant reductions in risk. Most antioxidants lost their effect when they were further adjusted for a term for all vegetables and fruits. beta-Carotene showed an increased risk with high intakes. On the other hand, vegetables and fruits remained as significant variables after adjustment for each antioxidant, suggesting that other substances or other mechanisms could explain this effect.

(-) F/V

Cancer: gastric

De Stefani E

Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay.

De Stefani E, Boffetta P, Brennan P, Deneo-Pellegrini H, Carzoglio JC, Ronco A, Mendilaharsu M.

Eur J Cancer Prev. 2000 Oct;9(5):329-34.

2000

In the period 1997-1999, 120 incident and histologically verified cases of stomach cancer were frequency matched on age, sex, residence and urban/rural status with 360 controls in order to study the role of diet in gastric cancer in Uruguay. Our attention was focused on the role of carotenoids in gastric carcinogenesis, after controlling for major confounders. According to the results, vitamin A, alpha-carotene and lycopene were associated with strong inverse relationships with stomach cancer (OR of stomach cancer for high alpha-carotene intake 0.34, 95% CI 0.17-0.65). Joint exposure to high intakes of alpha-carotene and vitamin C intakes were associated with a strong reduction in risk (OR 0.11, 95% CI 0.03-0.36). It was also suggested that high lycopene intake explained most of the reduction in risk of gastric cancer associated with vegetable intake, whereas no such effect was observed for fruit intake.

(-)

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: gastric

La Vecchia C

Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms

La Vecchia C

Exp Biol Med (Maywood). 2002 Nov;227(10):860-3.

2002

(-)

Cancer: gastric

Pelucchi C

Dietary intake of selected micronutrients and gastric cancer risk: an Italian case-control study.

Pelucchi C, Tramacere I, Bertuccio P, Tavani A, Negri E, La Vecchia C.

Ann Oncol. 2009 Jan;20(1):160-5. Epub 2008 Jul 31.

2009

BACKGROUND: A high consumption of non-starchy vegetables and fruits likely decreases the risk of gastric cancer, but no specific constituent of plant foods has been consistently identified to explain this association. PATIENTS AND METHODS: We considered several micronutrients and minerals in an Italian case-control study conducted between 1997 and 2007, including 230 patients with incident, histologically confirmed gastric cancer and 547 matched controls, admitted with acute conditions. Micronutrients computation was based on a validated and reproducible food frequency questionnaire, through an Italian food composition database. We estimated odds ratios (ORs) using conditional logistic regression, adjusted for energy intake and selected covariates. RESULTS: We found decreased ORs for the highest versus lowest quartile of vitamin E (OR=0.50), alpha-carotene (OR=0.52) and beta-carotene (OR=0.42) intake. Gastric cancer was directly associated with sodium, with ORs of 2.22 for the second, 2.56 for the third and 2.46 for the fourth quartile of intake. No significant relation emerged with iron, calcium, potassium, zinc, vitamin C, thiamin, riboflavin, niacin, vitamin B6, folate, vitamin D, retinol, beta-cryptoxanthin, lycopene and lutein plus zeaxanthin. CONCLUSIONS: Our data support a favourable effect on gastric cancer of vitamin E and selected carotenoids and a detrimental effect of sodium even at intermediate levels of intake.

Disease	First	Study Title and	Date	Abstract	Study	G.Tom	P.Tom	F.Tom	Lyco	Other
type	Author	Complete Citation			Type	+, N,	+, N,	+, N,	+, N,	+, N,
Cancer: gastric	Persson C	Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case-control study. Persson C, Sasazuki S, Inoue M, Kurahashi N, Iwasaki M, Miura T, Ye W, Tsugane S; JPHC Study Group. Carcinogenesis. 2008 May;29(5):1042-8. Epub 2008 Mar 13.	2008	Fruits and vegetables have been suggested to confer protection against diseases such as cancer through the effects of antioxidants, often represented by carotenoids. We investigated the impact of carotenoids, retinol and tocopherol on gastric cancer development in a large nested case-control study among Japanese with known Helicobacter pylori infection status. A total of 36 745 subjects aged 40-69 in the Japan Public Health Center-based Prospective Study who responded to the baseline questionnaire and provided blood samples in 1990-1995 were followed until 2004. Plasma levels of carotenoids in 511 gastric cancer cases and 511 matched controls were measured by high-performance liquid chromatography. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression models. Plasma level of beta-carotene was inversely associated with the risk of gastric cancer (compared with the lowest quartile: OR = 0.63, 95% CI = 0.31-0.75; OR = 0.48, 95% CI = 0.31-0.75 and OR = 0.46, 95% CI = 0.28-0.75, for quartile 2, 3 and 4, respectively, P(trend) < 0.01). Inverse associations were evident in men for alpha-carotene (P(trend) = 0.04) and beta-carotene (P(trend) < 0.01), but not in women, who had relatively higher plasma levels compared with men. We found no statistically significant association between plasma levels of lutein/zeaxanthin, lycopene, retinol, alpha- or gamma-tocopherol and gastric cancer risk. Our findings suggest that those who have very low plasma levels of alpha-carotene and beta-carotene are at a higher risk of gastric cancer.	CC from a PC				N
Cancer: gastric	Botterweck AA	Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up. Botterweck AA, van den Brandt PA, Goldbohm RA. Cancer. 2000 Feb 15;88(4):737-48.	2000	BACKGROUND: Numerous components of fruit and vegetables are considered to decrease the risk of gastric carcinoma. In the current prospective study, the authors examined the association between the intake of vitamins, carotenoids, and dietary fiber and vitamin supplement use and the incidence rate of gastric carcinoma. METHODS: The Netherlands Cohort Study began in 1986 with 120,852 men and women ages 55-69 years. Data regarding diet and other covariates were collected by means of a self-administered questionnaire. After 6.3 years of follow-up, data regarding 282 incident cases of gastric carcinoma and 3123 subcohort members were available for case-cohort analyses. RESULTS: In analyses adjusted for age, gender, smoking history, education, stomach disorders, and family history of gastric carcinoma, an inverse association with vitamin C intake (relative risk [RR] for highest vs. lowest intake category, 0.7; 95% confidence interval [95% CI], 0.5-1.0) was observed, with a borderline significant trend across three intake categories (P = 0. 06). After the exclusion of cases diagnosed in the first and second follow-up years, the RR was 0.9 (95% CI, 0.6-1.2; P trend = 0.44). Intake of retinol and beta-carotene were associated positively with gastric carcinoma risk with highest versus lowest quintile RRs of 1. 6 (95% CI, 1.0-2.5; P trend = 0.02) and 1.6 (95% CI, 1.0-2.6; P trend = 0.13), respectively, after the exclusion of first-year and second-year cases. Intake of folate, vitamin E, alpha-carotene, lutein plus zeaxanthin, beta-cryptoxanthin, lycopene, and dietary fiber was not associated with gastric carcinoma. Patients who used vitamin A-containing supplements had a lower risk of gastric carcinoma than nonusers (RR = 0.4; 95% CI, 0.2-0.9). CONCLUSIONS: No clear inverse associations were found between the intake of vitamins, carotenoids, and dietary fiber and the risk of gastric carcinoma after adjustment for confounding variables and the exclusion of first-year and second-year cases.	CC nested				N

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: gastric

Nouraie M

Fruits, vegetables, and antioxidants and risk of gastric cancer among male smokers.

Nouraie M, Pietinen P, Kamangar F, Dawsey SM, Abnet CC, Albanes D, Virtamo J, Taylor PR.

Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2087-92.

2005

The effect of consumption of fruits, vegetables, and antioxidants on the incidence of gastric cancer is inconclusive. In this prospective cohort study, we report the association of dietary intake of fruits, vegetables, antioxidants, and baseline serum levels of antioxidants with subsequent incidence of gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Participants of this study were 29,133 male smokers recruited into the alpha-Tocopherol, beta-Carotene Cancer Prevention study between 1985 and 1988. At baseline, a self-administered food use questionnaire with 276 food items was used to assess dietary intake. Baseline serum samples were stored at -70 degrees C. During a median follow-up of 12 years, 243 incident gastric adenocarcinomas (64 GCC and 179 GNCC) were diagnosed in this cohort, of whom 220 (57 GCC and 163 GNCC) had complete dietary information. For GCC, high dietary intake of retinol was protective [hazard ratio (HR), 0.46; 95% confidence interval (95% CI), 0.27-0.78], but high intake of alpha-tocopherol (HR, 2.06; 95% CI, 1.20-3.54) and gamma-tocopherol (HR, 1.94; 95% CI, 1.13-3.34) increased risk. For GNCC, higher intakes of fruits (HR, 0.51; 95% CI, 0.37-0.71), vitamin C (HR, 0.60; 95% CI, 0.41-0.86), alpha-tocopherol (HR, 0.78; 95% CI, 0.55-1.10), gamma-tocopherol (HR, 0.69; 95% CI, 0.49-0.96), and lycopene (HR, 0.67; 95% CI, 0.47-0.95) were protective. Our results suggest a difference in the effect of some of these exposures on GCC and GNCC. Tocopherols were associated with higher risk of GCC, whereas dietary intake of fruits, vitamin C, tocopherols, and lycopene seemed protective for GNCC.

(-)

Cancer: gastric

Maserejian NN

Prospective study of fruits and vegetables and risk of oral premalignant lesions in men.

Maserejian NN, Giovannucci E, Rosner B, Zavras A, Joshipura K.

Am J Epidemiol. 2006 Sep 15;164(6):556-66. Epub 2006 Jul 17.

2006

The authors prospectively evaluated fruit and vegetable consumption and the incidence of oral premalignant lesions among 42,311 US men in the Health Professionals Follow-up Study. Diet was assessed every 4 years by food frequency questionnaires. The authors confirmed 207 cases of clinically or histopathologically diagnosed oral premalignant lesions occurring between 1986 and 2002. Multivariate-adjusted relative risks were calculated from proportional hazards models. Significant inverse associations were observed with citrus fruits, citrus fruit juice, and vitamin-C-rich fruits and vegetables, indicating 30-40% lower risks with greater intakes (e.g., citrus fruit juice quintile 5 vs. quintile 1 relative risk = 0.65, 95% confidence interval: 0.42, 0.99). Inverse associations with fruits did not vary by smoking status and were stronger in analyses of baseline consumption, with a 10-year lag time to disease follow-up (quintile 5 vs. quintile 1 relative risk = 0.41, 95% confidence interval: 0.20, 0.82; p = 0.01). No associations were observed with total vegetables or with beta-carotene-rich or lycopene-rich fruits and vegetables. For current smokers, green leafy vegetables (ptrend = 0.05) and beta-carotene-rich fruits and vegetables (ptrend = 0.02) showed significant linear trends of increased risk (one additional serving/day relative risk = 1.7). The risk of oral premalignant lesions was significantly reduced with higher consumption of fruits, particularly citrus fruits and juices, while no consistent associations were apparent for vegetables.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N,

Lyco +, N,

Other +, N,

Cancer: gastric

Larsson SC

Vitamin A, retinol, and carotenoids and the risk of gastric cancer: a prospective cohort study.

Larsson SC, Bergkvist L, Naslund I, Rutegard J, Wolk A.

Am J Clin Nutr. 2007 Feb;85(2):497-503.

2007

BACKGROUND: Vitamin A may influence gastric carcinogenesis through its essential role in controlling cell proliferation and differentiation. However, epidemiologic studies of vitamin A, retinol (preformed vitamin A), and provitamin A carotenoids in relation to the risk of gastric cancer have documented inconsistent results.
OBJECTIVE: The objective of the study was to examine the associations between intakes of vitamin A, retinol, and specific carotenoids and the risk of gastric cancer in a prospective population-based cohort study of Swedish adults.
DESIGN: The study cohort consisted of 82 002 Swedish adults aged 45-83 y who had completed a food-frequency questionnaire in 1997. The participants were followed through June 2005.
RESULTS: During a mean 7.2-y follow-up, 139 incident cases of gastric cancer were diagnosed. High intakes of vitamin A and retinol from foods only (dietary intake) and from foods and supplements combined (total intake) and of dietary alpha-carotene and beta-carotene were associated with a lower risk of gastric cancer. The multivariate relative risks for the highest versus lowest quartiles of intake were 0.53 (95% CI: 0.32, 0.89; P for trend = 0.02) for total vitamin A, 0.56 (95% CI: 0.33, 0.95; P for trend = 0.05) for total retinol, 0.50 (95% CI: 0.30, 0.83; P for trend = 0.03) for alpha-carotene, and 0.55 (95% CI: 0.32, 0.94; P for trend = 0.07) for beta-carotene. No significant associations were found for beta-cryptoxanthin, lutein and zeaxanthin, or lycopene intake.
CONCLUSION: High intakes of vitamin A, retinol, and provitamin A carotenoids may reduce the risk of gastric cancer.

Cancer: gastric/ esoph

De Stefani E

Nutrient intake and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay.

De Stefani E, Ronco AL, Boffetta P, Deneo-Pellegrini H, Acosta G, Correa P, Mendilaharsu M.

Nutr Cancer. 2006;56(2):149-57.

2006

In 1996-2004 a case-control study on nutrient intake, dietary constituents and risk of squamous cell carcinoma of the esophagus was conducted in Montevideo, Uruguay. In fact, Uruguay, and especially its northern provinces, which border Brazil, are high-risk areas. The study included 234 cases and 936 controls. The controls were hospitalized patients with non-neoplastic disease, which was not related to tobacco smoking and alcohol drinking, and without recent changes in their diets. Controls were frequency matched to cases on age (10-yr intervals), sex, and residence (Montevideo and other provinces). Dietary constituents were energy adjusted using the residuals method and then categorized in quartiles according to the distribution of the controls. The final model included linoleic acid, lycopene, alpha-carotene, beta-cryptoxanthin, vitamin A, monounsaturated fat, total carbohydrates, beta-carotene, and folate. The odds ratio (OR) for high intake of linoleic acid was 1.4 (95% confidence interval, CI = 1.2-1.6), whereas lycopene displayed a strong protective effect (OR = 0.7; 95% CI = 0.6-0.9). The possible role of these and other dietary constituents in esophageal carcinogenesis is discussed.

(-) protective

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: gastric/or al

Maserejian NN

Prospective study of vitamins C, E, and A and carotenoids and risk of oral premalignant lesions in men.

Maserejian NN, Giovannucci E, Rosner B, Joshipura K.

Int J Cancer. 2007 Mar 1;120(5):970-7.

2007

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further. Copyright 2006 Wiley-Liss, Inc.

Cancer: lung

Le Marchand L

Intake of specific carotenoids and lung cancer risk.

Le Marchand L, Hankin JH, Kolonel LN, Beecher GR, Wilkens LR, Zhao LP.

Cancer Epidemiol Biomarkers Prev. 1993 May-Jun;2(3):183-7.

1993

Using newly available food composition data for carotenoids, the authors reanalyzed a population-based case-control study of diet and lung cancer conducted in Hawaii in 1983-1985 (L. Le Marchand et al., J. Natl. Cancer Inst., 81: 1158-1164, 1989). The analysis included interviews with 230 men and 102 women with lung cancer and 597 men and 268 women as controls, frequency-matched to the patients by age and sex. A previously validated quantitative diet history assessed the usual intake of foods rich in carotenoids. After adjusting for smoking and other covariates, no association was found with lung cancer risk for dietary lycopene or beta-cryptoxanthin intake, whereas dose-dependent inverse associations of comparable magnitude were found for dietary beta-carotene, alpha-carotene, and lutein. When subjects were cross-classified by their joint intakes of the latter three carotenoids, those who had a high intake (> median) for all three had the lowest risk for lung cancer. In a similar two-way interaction analysis, the previously reported inverse association of lung cancer with vegetable consumption in these data was found to be stronger than that with intake of these three carotenoids. Consistent with our previous findings, this analysis provides further evidence for a protective effect of certain carotenoids against lung cancer and for the greater protection afforded by consuming a variety of vegetables compared to only foods rich in a particular carotenoid.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: lung

Garcia-Closas R

Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain.

Garcia-Closas R, Agudo A, Gonzalez CA, Riboli E.

Nutr Cancer. 1998;32(3):154-8.

1998

Newly available data of a case-control study of lung cancer in women in Spain were analyzed to assess the relationship with the intake of specific carotenoids (alpha-carotene, beta-carotene, lutein, and lycopene) and flavonoids (quercetin, kaempferol, myricetin, and luteolin). The study included 103 cases and 206 hospital controls, matched by age and residence. Usual food intake was estimated through a food-frequency questionnaire. With adjustment for smoking habit and vitamin E, vitamin C, and total flavonoid intake, no association was found for the intake of alpha-carotene, beta-carotene, or lutein. The odds ratio (95% confidence interval) for women in the highest tertile of lycopene intake with respect to the lowest was 0.56 (0.26-1.24), with p for trend = 0.15. A nonsignificant association was observed for the highest vs. lowest tertile intake of kaempferol (odds ratio = 0.51, 95% confidence interval = 0.22-1.17), with p for trend = 0.10, after adjustment for smoking and vitamin E, vitamin C, and total carotenoid intake. No protective effect was observed for quercetin or luteolin or for total flavonoid intake.

Cancer: lung

Rohan TE

A cohort study of dietary carotenoids and lung cancer risk in women (Canada).

Rohan TE, Jain M, Howe GR, Miller AB.

Cancer Causes Control. 2002 Apr;13(3):231-7.

2002

OBJECTIVE: To investigate the association between dietary carotenoid intake and lung cancer risk in women. METHODS: A case-cohort study was undertaken in the Canadian National Breast Screening Study dietary cohort, which consists of 56,837 women who completed a self-administered dietary questionnaire. The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 196 cohort members were diagnosed with incident lung cancer. For analysis, a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 155 cases and 5,361 non-cases. RESULTS: When compared to those in the lowest quartile level of intake, the adjusted incidence rate ratios (95% confidence intervals) for those in the highest quartile levels of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein intake were 0.90 (0.51-1.58). 1.40 (0.76-2.59), 0.66 (0.33-1.32), 1.04 (0.61-1.76), and 1.26 (0.70-2.24), respectively; none of the associated tests for trend was statistically significant. CONCLUSION: These results suggest that there is no association between dietary carotenoid intake and lung cancer risk. At least for the range of intakes observed here.

CC nested

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: lung

Michaud DS

Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts.

Michaud DS, Feskanich D, Rimm EB, Colditz GA, Speizer FE, Willett WC, Giovannucci E.

Am J Clin Nutr. 2000 Oct;72(4):990-7.

2000

BACKGROUND: Carotenoids may reduce lung carcinogenesis because of their antioxidant properties; however, few studies have examined the relation between intakes of individual carotenoids and lung cancer risk. OBJECTIVE: The aim of this study was to examine the relation between lung cancer risk and intakes of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2 large cohorts. DESIGN: During a 10-y follow-up period, 275 new cases of lung cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases were diagnosed in 77283 women. Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up. The data were analyzed separately for each cohort and the results were pooled to compute overall relative risks (RRs).
RESULTS: In the pooled analyses, alpha-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer; the association with beta-carotene, lutein, and beta-cryptoxanthin intakes were inverse but not significant. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest compared with lowest total carotenoid score category). Inverse associations were strongest after a 4-8-y lag between dietary assessment and date of diagnosis. In subjects who never smoked, a 63% lower incidence of lung cancer was observed for the top compared with the bottom quintile of alpha-carotene intake (RR: 0.37; 95% CI: 0.18, 0.77).
CONCLUSION: Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

(-)

Cancer: lung

Voorrips LE

A prospective cohort study on antioxidant and folate intake and male lung cancer risk.

Voorrips LE, Goldbohm RA, Brants HA, van Poppel GA, Sturmans F, Hermus RJ, van den Brandt PA.

Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):357-65.

2000

Many studies have reported inverse associations between vegetable and fruit consumption and lung cancer risk. The aim of the present study was to elucidate the role of several antioxidants and folate in this relationship. In the Netherlands Cohort Study on Diet and Cancer, 58,279 men of ages 55-69 years at baseline in 1986 returned a questionnaire including a 150-item food frequency questionnaire. After 6.3 years of follow-up, 939 male lung cancer cases were registered. A new Dutch carotenoid database was used to estimate intake of alpha-carotene, beta-carotene, lutein + zeaxanthin, beta-cryptoxanthin, and lycopene, completed with the antioxidant vitamins C and E and folate. Using case-cohort analysis, rate ratios were calculated, adjusted for age, smoking, educational level, and family history of lung cancer. Protective effects on lung cancer incidence were found for lutein + zeaxanthin, beta-cryptoxanthin, folate, and vitamin C. Other carotenoids (alpha-carotene, beta-carotene, and lycopene) and vitamin E did not show significant associations. After adjustment for vitamin C, only folate remained inversely associated, and after adjustment for folate, only beta-cryptoxanthin and vitamin C remained significantly associated. Inverse associations were strongest among current smokers and weaker for former smokers at baseline. Inverse associations with carotenes, lutein + zeaxanthin, and beta-cryptoxanthin seemed to be limited to small cell and squamous cell carcinomas. Only folate and vitamin C intake appeared to be inversely related to small cell and squamous cell carcinomas and adenocarcinomas. Folate, vitamin C, and beta-cryptoxanthin might be better protective agents against lung cancer in smokers than alpha-carotene, beta-carotene, lutein + zeaxanthin, and lycopene.

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N,

Lyco +, N,

Other +, N,

Cancer: lung

Holick CN

Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study.

Holick CN, Michaud DS, Stolzenberg-Solomon R, Mayne ST, Pietinen P, Taylor PR, Virtamo J, Albanes D.

Am J Epidemiol. 2002 Sep 15;156(6):536-47.

2002

Findings from several beta-carotene supplementation trials were unexpected and conflicted with most observational studies. Carotenoids other than beta-carotene are found in a variety of fruits and vegetables and may play a role in this important malignancy, but previous findings regarding the five major carotenoids are inconsistent. The authors analyzed the associations between dietary beta-carotene, beta-carotene, lutein/zeaxanthin, lycopene, beta-cryptoxanthin, vitamin A, serum beta-carotene, and serum retinol and the lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers conducted in southwestern Finland between 1985 and 1993. Of the 27,084 male smokers aged 50-69 years who completed the 276-food item dietary questionnaire at baseline, 1,644 developed lung cancer during up to 14 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Consumption of fruits and vegetables was associated with a lower lung cancer risk (relative risk = 0.73, 95% confidence interval: 0.62, 0.86, highest vs. lowest quintile). Lower risks of lung cancer were observed for the highest versus the lowest quintiles of lycopene (28%), lutein/zeaxanthin (17%), beta-cryptoxanthin (15%), total carotenoids (16%), serum beta-carotene (19%), and serum retinol (27%). These findings suggest that high fruit and vegetable consumption, particularly a diet rich in carotenoids, tomatoes, and tomato-based products, may reduce the risk of lung cancer.

(-)

Cancer: ovarian

Cramer DW

Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women.

Cramer DW, Kuper H, Harlow BL, Titus-Ernstoff L.

Int J Cancer. 2001 Oct 1;94(1):128-34.

2001

An inverse association between ovarian cancer risk, carotenoids and antioxidant vitamins has been suggested by several epidemiologic studies and 1 experimental trial of a vitamin A analogue. From a population-based study of 549 cases of ovarian cancer and 516 controls, we estimated the consumption of the antioxidant vitamins A, C, D and E and various carotenoids, including alpha- and beta-carotene and lycopene, using a validated dietary questionnaire. Multivariate logistic regression was used to calculate the exposure odds ratios adjusted for established ovarian cancer risk factors. Intakes of carotene, especially alpha-carotene, from food and supplements were significantly and inversely associated with risk for ovarian cancer, predominantly in postmenopausal women. Intake of lycopene was significantly and inversely associated with risk for ovarian cancer, predominantly in premenopausal women. Food items most strongly related to decreased risk for ovarian cancer were raw carrots and tomato sauce. Consumption of fruits, vegetables and food items high in carotene and lycopene may reduce the risk of ovarian cancer.

(-)

(-) pre-meno

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: ovarian

La Vecchia C

Tomatoes, lycopene intake, and digestive tract and female hormone-related neoplasms

La Vecchia C

Exp Biol Med (Maywood). 2002 Nov;227(10):860-3.

2002

Cancer: ovarian

Zhang M

Intake of specific carotenoids and the risk of epithelial ovarian cancer.

Zhang M, Holman CD, Binns CW.

Br J Nutr. 2007 Jul;98(1):187-93. Epub 2007 Mar 19.

2007

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, few studies have examined the association between intake of specific carotenoids and the risk of epithelial ovarian cancer and the results for carotenoids have been inconclusive. To investigate whether the intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and lycopene is inversely associated with ovarian cancer risk, a case-control study was conducted in China during 1999-2000. The cases were 254 patients with histologically confirmed epithelial ovarian cancer and 652 age-matched controls were randomly recruited during the same period. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable FFQ. The US Department of Agriculture nutrient composition database was used to calculate the intake of specific carotenoids. Unconditional logistic regression analyses were used to estimate OR and 95 % CI, accounting for age, locality, education, BMI, smoking, tea drinking, parity, oral contraceptive use, hormone replacement therapy, menopausal status, family history of ovarian cancer, physical activity and energy intake. Compared with the highest v. the lowest quartile of intake, the adjusted OR were 0.39 (95 % CI 0.23, 0.66) for alpha-carotene, 0.51 (95 % CI 0.31, 0.84) for beta-carotene, 0.51 (95 % CI 0.31, 0.83) for beta-cryptoxanthin, 0.45 (0.27, 0.76) for lutein and zeaxanthin, and 0.33 (95 % CI 0.20, 0.56) for total carotenoids, with statistically significant tests for trend. It is concluded that a higher intake of carotenoids can reduce the risk of epithelial ovarian cancer.

(-)

↓ risk

total carot-enoids

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N,

Lyco +, N,

Other +, N,

Cancer: ovarian

Koushik A

Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies.

Koushik A, Hunter DJ, Spiegelman D, Anderson KE, Buring JE, Freudenheim JL, Goldbohm RA, Hankinson SE, Larsson SC, Leitzmann M, Marshall JR, McCullough ML, Miller AB, Rodriguez C, Rohan TE, Ross JA, Schatzkin A, Schouten LJ, Willett WC, Wolk A, Zhang SM, Smith-Warner SA.

Int J Cancer. 2006 Nov 1;119(9):2148-54.

2006

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 microg/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 microg/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 microg/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 microg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 microg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer.

Cancer: pancreati c

Nkondjock A

Dietary intake of lycopene is associated with reduced pancreatic cancer risk. Nkondjock A, Ghadirian P, Johnson KC, Krewski D; Canadian Cancer Registries Epidemiology Research Group. J Nutr. 2005 Mar;135(3):592-7.

2005

Although fruits and vegetables have been implicated in the etiology of pancreatic cancer, the role of phytochemicals in these food groups has received little attention to date. In this study, we investigated the possible association between dietary carotenoids and pancreatic cancer risk. A case-control study of 462 histologically confirmed pancreatic cancer cases and 4721 population-based controls in 8 Canadian provinces took place between 1994 and 1997. Dietary intake was assessed by a self-administered FFQ. Unconditional logistic regression was used to assess associations between specific and total carotenoid intakes and the risk of pancreatic cancer. All tests of statistical significance were 2-sided. After adjustment for age, province, BMI, smoking, educational attainment, dietary folate, and total energy intake, lycopene, provided mainly by tomatoes, was associated with a 31% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.69; 95% CI: 0.46-0.96; P = 0.026 for trend] when comparing the highest and lowest quartiles of intake. Both beta-carotene (OR = 0.57; 95% CI: 0.32-0.99; P = 0.016 for trend) and total carotenoids (OR = 0.58; 95% CI: 0.34-1.00; P = 0.02 for trend) were associated with a significantly reduced risk among those who never smoked. The results of this study suggest that a diet rich in tomatoes and tomato-based products with high lycopene content may help reduce pancreatic cancer risk.

(-)

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	Lyco +, N,
Cancer: prostate	Key TJ	A case-control study of diet and prostate cancer. Key TJ, Silcocks PB, Davey GK, Appleby PN, Bishop DT. Br J Cancer. 1997;76(5):678-87.	1997	We interviewed 328 men diagnosed with prostate cancer before the age of 75 years and 328 age-matched population controls. The principal hypotheses were that risk would increase with a high intake of total or saturated fat and would decrease with a high intake of carotene (beta-carotene equivalents) or lycopene. We also examined the associations of other nutrients and foods with risk. There was no evidence for an association between fat intake and risk, although the average fat intake was high and the range of fat intakes was narrow (medians of lower and upper thirds of percentage of energy from fat among controls were 34.3% and 42.9% respectively). Risk was lower in subjects with higher carotene intake: odds ratios 0.65 (95% CI 0.45-0.94) and 0.76 (0.53-1.10) in the middle and upper thirds of carotene intake respectively (P for trend = 0.150). Lycopene was not associated with risk. Among 13 other nutrients examined, the odds ratios in the top third of intake were below 0.8 for: potassium, 0.74 (0.51-1.09; P for trend = 0.054); zinc, 0.73 (0.49-1.08; P for trend = 0.126); iodine, 0.75 (0.51-1.11; P for trend = 0.077); vitamin B6 food only, 0.77 (0.53-1.12; P for trend = 0.077); and vitamin B6 including supplements, 0.70 (0.48-1.03; P for trend = 0.029). Among 18 foods examined, statistically significant associations were observed for: garlic as food, > or = 2/week vs never, 0.56 (0.33-0.93); garlic including supplements, > or = 2/week vs never, 0.60 (0.37-0.96); baked beans, > or = 2/week vs < 1/month, 0.57 (0.34-0.95); and garden peas, > or = 5/week vs < or = 3/month, 0.35 (0.13-0.91). This study does not support the hypothesis that fat increases risk and is equivocal in relation to carotene. The possible relationships of vitamin B6, garlic, beans and peas with risk for prostate cancer should be further investigated.	CC	N
Cancer: prostate	Vogt TM	Dietary factors and risks for prostate cancer among blacks and whites in the United States. Vogt TM, Mayne ST, Graubard BI, Swanson CA, Sowell AL, Schoenberg JB, Swanson GM, Greenberg RS, Hoover RN, Hayes RB, Ziegler RG. Cancer Epidemiol Biomarkers Prev. 1999 Jan;8(1):25-34.	1999	Prostate cancer is the most common malignancy in men in the United States, with substantially higher rates among American blacks than whites. We carried out a population-based case-control study in three geographic areas of the United States to evaluate the reasons for the racial disparity in incidence rates. A total of 932 men (449 black men and 483 white men) who had been newly diagnosed with pathologically confirmed prostate cancer and 1201 controls (543 black men and 658 white men) were interviewed in person to elicit information on potential risk factors. This report evaluates the impact of dietary factors, particularly the consumption of animal products and animal fat, on the risk of prostate cancer among blacks and whites in the United States. Increased consumption (grams/day) of foods high in animal fat was linked to prostate cancer (independent of intake of other calories) among American blacks [by quartile of intake, odds ratio (OR) = 1.0 (referent), 1.5, 2.1, and 2.0; Ptrend = 0.007], but not among American whites [by quartile of intake, OR = 1.0 (referent), 1.6, 1.5, and 1.1; Ptrend = 0.90]. However, risks for advanced prostate cancer were higher with greater intake of foods high in animal fat among blacks [by quartile of intake, OR = 1.0 (referent), 2.2, 4.2, and 3.1; Ptrend = 0.006] and whites [by quartile of intake, OR = 1.0 (referent), 2.2, 2.6, and 2.4; Ptrend = 0.02]. Increased intake of animal fat as a proportion of total caloric intake also showed positive but weaker associations with advanced prostate cancer among blacks (Ptrend = 0.13) and whites (Ptrend = 0.08). No clear associations were found with vitamin A, calcium, or specific lycopene-rich foods. The study linked greater consumption of fat from animal sources to increased risk for prostate cancer among American blacks and to advanced prostate cancer among American blacks and whites. A reduction of fat from animal sources in the diet could lead to decreased incidence and mortality rates for prostate cancer, particularly among American blacks.	CC	N

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Cancer: prostate	Norrish AE	Prostate cancer and dietary carotenoids. Norrish AE, Jackson RT, Sharpe SJ, Skeaff CM. Am J Epidemiol. 2000 Jan 15;151(2):119-23.	2000	This population-based case-control study investigated associations between prostatecancer risk and dietary intake of the carotenoids beta-carotene and lycopene and their major plant food sources, including carrots, green leafy vegetables, and tomato-based foods. The study was carried out in Auckland, New Zealand, during 1996-1997 and recruited 317 prostate cancer cases and 480 controls. The authors found that dietary intake of beta-carotene and its main vegetable sources was largely unassociated with prostate cancer risk, whereas intake of lycopene and tomato-based foods was weakly associated with a reduced risk. These results suggest that in contrast to the findings regarding many types of cancers, vegetables rich in beta-carotene are not protective against prostate cancer. However, lycopene from tomato-based foods was found to be associated with a small reduction in risk.	CC	(-)			(-)
Cancer: prostate	Jian L	Do dietary lycopene and other carotenoids protect against prostate cancer? Jian L, Du CJ, Lee AH, Binns CW. Int J Cancer. 2005 Mar 1;113(6):1010-4.	2005	To determine whether dietary intake of lycopene and other carotenoids has an etiological association with prostate cancer, a case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases. Information on usual food consumption, including vegetables and fruits, was collected by face-to-face interviews using a structured food frequency questionnaire. The risks of prostate cancer for the intake of carotenoids and selected vegetables and fruits rich in carotenoids were assessed using multivariate logistic regression, adjusting for age, locality, education, income, body mass index, marital status, number of children, family history of prostate cancer, tea drinking, total fat and caloric intake. The prostate cancer risk declined with increasing consumption of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin. Intake of tomatoes, pumpkin, spinach, watermelon and citrus fruits were also inversely associated with the prostate cancer risk. The adjusted odds ratios for the highest versus the lowest quartiles of intake were 0.18 (95% CI: 0.08-0.41) for lycopene, 0.43 (95% CI: 0.21-0.85) for alpha-carotene, 0.34 (95% CI: 0.17-0.69) for beta-carotene, 0.15 (95% CI: 0.06-0.34) for beta-cryptoxanthin and 0.02 (95% CI: 0.01-0.10) for lutein and zeaxanthin. The corresponding dose-response relationships were also significant, suggesting that vegetables and fruits rich in lycopene and other carotenoids may be protective against prostate cancer.	CC	(-) ↓ risk prostate cancer			(-) ↓ risk prostate cancer

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: prostate

Goodman M

Lycopene intake and prostate cancer risk: effect modification by plasma antioxidants and the XRCC1 genotype.

Goodman M, Bostick RM, Ward KC, Terry PD, van Gils CH, Taylor JA, Mandel JS.

Nutr Cancer. 2006;55(1):13

2006

Lycopene has been associated with reduced prostate cancer risk, although the results of epidemiological studies have varied. We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-control study of prostate cancer in North Carolina. Plasma alpha-tocopherol and beta-carotene levels were measured using high-performance liquid chromatography. XRCC1 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. The final dataset included 77 cases and 174 controls with complete questionnaires, genotyping, and plasma analyses. Among men with the Arg/Arg genotype at codon 399, odds ratios (ORs) for prostate cancer risk associated with medium (732-1,529 microg/day) and high (>1,529 microg/day) lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06-0.71), respectively (P(trend) < 0.01). Similar analyses for persons with Arg/Gln or Gln/Gln genotypes produced null results. Above-median (1,048 microg/day) lycopene intake combined with above-median levels of alpha-tocopherol and beta-carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg genotype but not those with at least one Gln allele (P(interaction) = 0.01). Although limited by small sample size, these findings indicate that the association between lycopene and prostate cancer is complex and may be modified by other antioxidants and by XRCC1 genotype.

(-)

↓ risk if have XRCC1 genotype and ↑ lyco intake

Cancer: prostate

Jian L

Tea and lycopene protect against prostate cancer.

Jian L, Lee AH, Binns CW.

Asia Pac J Clin Nutr. 2007;16 Suppl 1:453-7.

2007

Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men. Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake.

(-)

↓ risk and with green tea ↓↓ risk

Disease	First	Study Title and	Date	Abstract	Study	G.Tom	P.Tom	F.Tom	Lyco	Other
type	Author	Complete Citation			Type	+, N,	+, N,	+, N,	+, N,	+, N,
Cancer: prostate	Pourmand G	The risk factors of prostate cancer: a multicentric case-control study in Iran. Pourmand G, Salem S, Mehrsai A, Lotfi M, Amirzargar MA, Mazdak H, Roshani A, Kheirollahi A, Kalantar E, Baradaran N, Saboury B, Allameh F, Karami A, Ahmadi H, Jahani Y. Asian Pac J Cancer Prev. 2007 Jul-Sep;8(3):422-8.	2007	Prostate cancer (PC), in Iran, is the third most frequently diagnosed visceral cancer among men and the seventh most common underlying cause of cancer mortality. We evaluated the relation between speculated factors and PC risk using data from a multicentric case-control study conducted in Iran from 2005 to 2007 on 130 cases of incident, clinicopathologically confirmed PC, and 75 controls admitted to the same network of hospitals without any malignant disease. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression models. The risk of PC was increased with aging (OR: 5.35, 95% CI: 2.17-13.19; P<0.0001), and with the number of sexual intercourse >or=2 times/week (OR: 3.14, 95% CI: 1.2-8.2; P=0.02). One unit elevation in serum estradiol and testosterone concentration was related to increase (OR: 1.04, 95% CI: 1.01-1.06; P=0.006) and decrease (OR: 0.79; 95% CI: 0.64-0.96; P=0.02) of PC risk, respectively. Cases were less likely to have a history of diabetes (OR: 0.34, 95% CI: 0.12-0.98; P=0.04). Increasing in dietary consumption of lycopene and fat was associated with declined (OR: 0.45, 95% CI: 0.09-2.12) and increased (OR: 2.38, 95% CI: 0.29-19.4) PC development, respectively. Other factors including educational level, marriage status, dietary meat consumption, vasectomy and smoking have not been shown to affect PC risk in the Iranian population. Our study adds further information on the potential risk factors of PC and is the first epidemiologic report from Iran. However, justification of these results requires more well-designed studies with a larger number of participants.	CC				N
Cancer: prostate	Giovannucci E	A prospective study of tomato products, lycopene, and prostate cancer risk. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. J Natl Cancer Inst. 2002 Mar 6;94(5):391-8.	2002	BACKGROUND: Some data, including our findings from the Health Professionals Follow-Up Study (HPFS) from 1986 through January 31, 1992, suggest that frequent intake of tomato products or lycopene, a carotenoid from tomatoes, is associated with reduced risk of prostate cancer. Overall, however, the data are inconclusive. We evaluated additional data from the HPFS to determine if the association would persist. METHODS: We ascertained prostate cancer cases from 1986 through January 31, 1998, among 47 365 HPFS participants who completed dietary questionnaires in 1986, 1990, and 1994. We used pooled logistic regression to compute multivariate relative risks (RR) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From 1986 through January 31, 1998, 2481 men in the study developed prostate cancer. Results for the period from 1992 through 1998 confirmed our previous findings---that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84; 95% CI = 0.73 to 0.96; P(trend) =.003); intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77; 95% CI = 0.66 to 0.90; P(trend)<.001), especially for extraprostatic cancers (RR = 0.65; 95% CI = 0.42 to 0.99). These associations persisted in analyses controlling for fruit and vegetable consumption and for olive oil use (a marker for Mediterranean diet) and were observed separately in men of Southern European or other Caucasian ancestry. CONCLUSION: Frequent consumption of tomato products is associated with a lower risk of prostate cancer. The magnitude of the association was moderate enough that it could be missed in a small study or one with substantial errors in measurement or based on a single dietary assessment.	PC	(-)	(-)		(-)

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: prostate

Schuurman AG

A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands).

Schuurman AG, Goldbohm RA, Brants HA, van den Brandt PA.

Cancer Causes Control. 2002 Aug;13(6):573-82.

2003

OBJECTIVES: The roles of retinol, vitamins C and E, and carotenoids as risk factors for prostate carcinoma are still questionable. We evaluated these in the Netherlands Cohort Study.
METHODS: The cohort study consisted of 58,279 men ages 55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intakes of retinol, vitamins C and E, and several carotenoids were measured by means of a 150-item semi-quantitative food-frequency questionnaire.
RESULTS: In multivariate analyses a positive association with prostate cancer risk was observed for intake of betacryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94, 1.01, 1.16, 1.41; p-trend < 0.01. For intake of retinol, vitamins C and E and other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for vitamin supplement use were decreased, but not significantly. Among nondrinkers, nonsignificant inverse associations were observed for intake of retinol, alpha-carotene, and beta-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60, and 0.76, respectively). Among drinkers, beta-cryptoxanthin was positively associated (RR highest vs lowest quintile = 1.40).
CONCLUSIONS: These data show a positive association between beta-cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol, alpha-carotene, and beta-carotene among nondrinkers; this suggests an interaction between vitamins and alcohol consumption, which needs confirmation. Lycopene was not associated with prostate cancer.

Cancer: prostate

Kristal AR

Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial.

Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF, Thompson IM.

Am J Epidemiol. 2008 Apr 15;167(8):925-34. Epub 2008 Feb 7.

2008

This study examined dietary risk factors for incident benign prostatic hyperplasia (BPH) in 4,770 Prostate Cancer Prevention Trial (1994-2003) placebo-arm participants who were free of BPH at baseline. BPH was assessed over 7 years and was defined as medical or surgical treatment or repeated elevation (>14) on the International Prostate Symptom Score questionnaire. Diet, alcohol, and supplement use were assessed by use of a food frequency questionnaire. There were 876 incident BPH cases (33.6/1,000 person-years). The hazard ratios for the contrasts of the highest to lowest quintiles increased 31% for total fat and 27% for polyunsaturated fat and decreased 15% for protein (all p(trend) < 0.05). The risk was significantly lower in high consumers of alcoholic beverages (0 vs. > or =2/day: hazard ratio (HR) = 0.67) and vegetables (<1 vs. > or =4/day: HR = 0.68) and higher in daily (vs. <1/week) consumers of red meat (HR = 1.38). There were no associations of supplemental antioxidants with risk, and there was weak evidence for associations of lycopene, zinc, and supplemental vitamin D with reduced risk. A diet low in fat and red meat and high in protein and vegetables, as well as regular alcohol consumption, may reduce the risk of symptomatic BPH.

N BPH

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N, -

Lyco +, N,

Other +, N,

Cancer: renal

Bosetti C

Micronutrients and the risk of renal cell cancer: a case-control study from Italy.

Bosetti C, Scotti L, Maso LD, Talamini R, Montella M, Negri E, Ramazzotti V, Franceschi S, La Vecchia C.

Int J Cancer. 2007 Feb 15;120(4):892-6.

2007

The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41-0.75), and vitamin C (OR = 0.72, 95% CI = 0.54-0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59-1.08) for retinol, 0.82 (95% CI = 0.61-1.10) for alpha-carotene, 0.90 (95% CI = 0.68-1.20) for beta-carotene, 0.94 (95% CI = 0.73-1.21) for beta-criptoxanthin, 0.85 (95% CI = 0.63-1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57-1.01) for vitamin D, 0.75 (95% CI = 0.55-1.01) for thiamine, 0.88 (95% CI = 0.66-1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64-1.13), 0.85 (95% CI = 0.64-1.12) for folate and 0.80 (95% CI = 0.60-1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC.

Cancer: renal

Lee JE

Intakes of fruit, vegetables, and carotenoids and renal cell cancer risk: a pooled analysis of 13 prospective studies.

Lee JE, Mannisto S, Spiegelman D, Hunter DJ, Bernstein L, van den Brandt PA, Buring JE, Cho E, English DR, Flood A, Freudenheim JL, Giles GG, Giovannucci E, Hakansson N, Horn-Ross PL, Jacobs EJ, Leitzmann MF, Marshall JR, McCullough ML, Miller AB, Rohan TE, Ross JA, Schatzkin A, Schouten LJ, Virtamo J, Wolk A, Zhang SM, Smith-Warner SA.

2009

Fruit and vegetable consumption has been hypothesized to reduce the risk of renal cell cancer. We conducted a pooled analysis of 13 prospective studies, including 1,478 incident cases of renal cell cancer (709 women and 769 men) among 530,469 women and 244,483 men followed for up to 7 to 20 years. Participants completed a validated food-frequency questionnaire at baseline. Using the primary data from each study, the study-specific relative risks (RR) were calculated using the Cox proportional hazards model and then pooled using a random effects model. We found that fruit and vegetable consumption was associated with a reduced risk of renal cell cancer. Compared with <200 g/d of fruit and vegetable intake, the pooled multivariate RR for >or=600 g/d was 0.68 [95% confidence interval (95% CI) = 0.54-0.87; P for between-studies heterogeneity = 0.86; P for trend = 0.001]. Compared with <100 g/d, the pooled multivariate RRs (95% CI) for >or=400 g/d were 0.79 (0.63-0.99; P for trend = 0.03) for total fruit and 0.72 (0.48-1.08; P for trend = 0.07) for total vegetables. For specific carotenoids, the pooled multivariate RRs (95% CIs) comparing the highest and lowest quintiles were 0.87 (0.73-1.03) for alpha-carotene, 0.82 (0.69-0.98) for beta-carotene, 0.86 (0.73-1.01) for beta-cryptoxanthin, 0.82 (0.64-1.06) for lutein/zeaxanthin, and 1.13 (0.95-1.34) for lycopene. In conclusion, increasing fruit and vegetable consumption is associated with decreasing risk of renal cell cancer; carotenoids present in fruit and vegetables may partly contribute to this protection.

PC pooled

Disease type

First Author

Study Title and Complete Citation

Date

Abstract

Study Type

G.Tom +, N,

P.Tom +, N,

F.Tom +, N,

Lyco +, N,

Other +, N,

Cancer: uterine

Terry KL

Lycopene and other carotenoid intake in relation to risk of uterine leiomyomata. Terry KL, Missmer SA, Hankinson SE, Willett WC, De Vivo I. Am J Obstet Gynecol. 2008 Jan;198(1):37.e1-8. Epub 2007 Nov 5.

2008

OBJECTIVE: Carotenoids have antioxidant properties and have been associated with reduced risks of some cancers. We hypothesized that carotenoid intake may reduce the risk of diagnosed uterine leiomyoma (UL). STUDY DESIGN: We evaluated the associations between dietary carotenoids and risk of diagnosed UL in 82,512 premenopausal women aged 26-46 years in 1991 in the Nurses' Health Study II over 10 years of follow-up. Diet was assessed every 4 years with a validated food frequency questionnaire, and incidence of UL was assessed biennially by questionnaire.
RESULTS: Total lycopene intake was not associated with diagnosed UL risk. Intake of beta-carotene was associated with slightly increased risks of diagnosed UL; this association was restricted to current smokers (for highest vs lowest quintile, relative risk = 1.36, 95% confidence interval 1.05 to 1.76; P(trend) = .003).
CONCLUSION: Overall, our findings do not suggest that carotenoids reduce the risk of diagnosed UL. Among current smokers, high intake of beta-carotene may slightly increase risk of diagnosed UL.

Cancer: Mortality

Agudo A

Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality in Spanish adults: findings from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain).

Agudo A, Cabrera L, Amiano P, Ardanaz E, Barricarte A, Berenguer T, Chirlaque MD, Dorronsoro M, Jakszyn P, Larranaga N, Martinez C, Navarro C, Quiros JR, Sanchez MJ, Tormo MJ, Gonzalez CA.

Am J Clin Nutr. 2007 Jun;85(6):1634-42.

2007

BACKGROUND: Epidemiologic data suggest that persons with diets rich in fruit and vegetables are at a lower risk of several chronic diseases and mortality than are persons with diets poor in fruit and vegetables. Often, this effect is attributed to antioxidant micronutrients found in plant foods. OBJECTIVE: We aimed to assess the relation of mortality to the consumption of fruit, vegetables, and other plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids. DESIGN: The study was a prospective study in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up, 562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards regression analysis was used to assess the relation between dietary factors and total mortality. RESULTS: After adjustment for age, sex, and several potential confounders, the hazard ratio for the highest versus the lowest quartile of consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit, 0.72 (0.56, 0.91; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98; P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the "fruit" part of the plant, the seeds). The corresponding figures for antioxidant nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53, 0.87; P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51, 0.84; P for trend 0.001) for lycopene. The effect of vitamin C and provitamin A disappeared after adjustment for total antioxidant capacity in plant foods. CONCLUSIONS: A high intake of fresh fruit, root vegetables, and fruiting vegetables is associated with reduced mortality, probably as a result of their high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant capacity could partly explain the effect of ascorbic acid and provitamin A but not the association with lycopene.

(-)

Disease type	First Author	Study Title and Complete Citation	Date	Abstract	Study Type	G.Tom +, N,	P.Tom +, N,	F.Tom +, N, -	Lyco +, N,	Other +, N,
Cancer: Mortality	Agudo A	Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality in Spanish adults: findings from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). Agudo A, Cabrera L, Amiano P, Ardanaz E, Barricarte A, Berenguer T, Chirlaque MD, Dorronsoro M, Jakszyn P, Larranaga N, Martinez C, Navarro C, Quiras JR, Sanchez MJ, Tormo MJ, Gonzalez CA. Demark-Wahnefried W. Curr Urol Rep. 2008 May; 9(3):217-25.	2008	BACKGROUND: Epidemiologic data suggest that persons with diets rich in fruit and vegetables are at a lower risk of several chronic diseases and mortality than are persons with diets poor in fruit and vegetables. Often, this effect is attributed to antioxidant micronutrients found in plant foods. OBJECTIVE: We aimed to assess the relation of mortality to the consumption of fruit, vegetables, and other plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids. DESIGN: The study was a prospective study in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up, 562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards regression analysis was used to assess the relation between dietary factors and total mortality. RESULTS: After adjustment for age, sex, and several potential confounders, the hazard ratio for the highest versus the lowest quartile of consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit, 0.72 (0.56, 0.91; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98; P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the "fruit" part of the plant, the seeds). The corresponding figures for antioxidant nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53, 0.87; P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51, 0.84; P for trend 0.001) for lycopene. The effect of vitamin C and provitamin A disappeared after adjustment for total antioxidant capacity in plant foods. CONCLUSIONS: A high intake of fresh fruit, root vegetables, and fruiting vegetables is associated with reduced mortality, probably as a result of their high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant capacity could partly explain the effect of ascorbic acid and provitamin A but not the association with lycopene.	PC				(-) ↓ mortality

Cancer Critical Findings - Dietary Lycopene and Disease Risk

Cancer
Critical Findings - Dietary Lycopene and Disease Risk