Fruit and vegetable consumption in relation to ovarian cancer incidence: the Swedish Mammography Cohort

We prospectively examined the incidence of epithelial ovarian cancer and its subtypes in relation to baseline fruit and vegetable consumption in the Swedish Mammography Cohort, a population-based cohort study of 61 084 women aged 38-76 years in 1987-1990. During an average follow-up of 13.5 years, 266 incident cases of invasive epithelial ovarian cancer were diagnosed. After adjustment for potential confounders, we observed a statistically significant inverse association between consumption of vegetables and ovarian cancer risk (P-value for trend=0.01); the multivariate rate ratio (RR) for the comparison of three or more servings of vegetables per day with one or fewer servings per day was 0.61 (95% confidence interval (CI), 0.38-0.97). For fruit consumption a modest, not statistically significant, positive association was found (P-value for trend=0.07); the multivariate RR for the highest compared with the lowest category of consumption being 1.37 (95% CI, 0.90-2.06). The associations with fruit and vegetable consumption did not vary by subtype of ovarian cancer. These findings suggest that high consumption of vegetables, but not of fruits, may reduce the risk of ovarian cancer.     

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.     

Dietary folate and folate vitamers and the risk of prostate cancer in The Netherlands Cohort Study

Purpose

The aim of the present study was to examine the association between intake of folate, and specific folate vitamers, and the risk of advanced and total prostate cancer.

Methods

The association between dietary folate and prostate cancer risk was evaluated in The Netherlands Cohort Study (NLCS) on diet and cancer, conducted among 58,279 men ages 55–69?years at baseline. Information on diet was collected at baseline by means of food frequency questionnaires. Incident cases were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. After 17.3?years of follow-up, 3,669 incident prostate cancer cases, of which 1,290 advanced cases, and 2,336 male subcohort members were available for case-cohort analyses.

Results

Dietary folate was not associated with prostate cancer risk, nor with the risk of advanced prostate cancer, among men in the NLCS cohort (HR?=?1.05, 95?% CI: 0.87–1.26 and HR?=?1.09, 95?% CI: 0.88–1.35, respectively, for the highest quintile of folate intake vs. the lowest quintile). Specific folate vitamers were neither associated with the risk of prostate cancer or risk of advanced prostate cancer.

Conclusions

Our results do not support an association of dietary folate or specific folate vitamers on the risk of prostate cancer, or advanced prostate cancer.     

Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study

Folate is involved in DNA synthesis, repair, and methylation. It has been hypothesized that high intake of folate may reduce the risk of human cancers, including cancer of the breast. Using data from a population-based case-control study of breast cancer conducted in urban Shanghai during 1996-1998, we evaluated the association of dietary folate intake and breast cancer risk among 1321 cases and 1382 controls, 25-64 years of age, who never drank alcohol regularly or used vitamin supplements. Usual dietary habits were assessed with an in-person, interviewer-administered food frequency questionnaire developed and tested for use in this population. Unconditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (95% CIs) after adjusting for potential confounding factors. Dietary folate intake was inversely associated with breast cancer risk (P for trend, 0.05) with an adjusted OR of 0.71 (95% CI, 0.56-0.92) observed among women who were in the highest quintile of intake. The inverse association was stronger after further adjusting for total fruit and vegetable and animal food intakes (OR, 0.62; 95% CI, 0.46-0.82; P for trend, 0.01). A more pronounced inverse association between folate intake and breast cancer risk (OR, 0.47; 95% CI, 0.25-0.88; P for trend, 0.01) was observed among women who consumed high levels of folate cofactors (methionine, vitamin B(12), and vitamin B(6)) than those whose intake levels of these nutrients were low. Dietary intake of methionine, vitamin B(12), and vitamin B(6) were not independently related to risk of breast cancer after adjusting for confounding factors. Thus, our study adds additional support to the protective role of dietary folate in breast carcinogenesis and suggests further that the effect of folate may be modified by dietary intake of methionine, vitamin B(12), and vitamin B(6).     

An estrogen‐associated dietary pattern and breast cancer risk in the Swedish Mammography Cohort

High endogenous hormone levels have been associated with breast cancer and dietary factors have the potential to influence breast cancer risk through effects on hormone levels. Dietary patterns derived from reduced rank regression provide a way to identify food groups correlated with hormones and subsequently examine food patterns that may be associated with breast cancer risk. We investigated whether a dietary pattern previously correlated with estradiol and estrone sulfate was associated with breast cancer in the prospective Swedish Mammography Cohort. Among 37,004 primarily postmenopausal women diet was assessed with a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow‐up 1,603 cases of breast cancer were identified. A higher estrogen dietary pattern score was associated with an increased risk of breast cancer. Women in the highest quartile of estrogen pattern score had a 29% (95% CI = 1.08–1.55) increased risk of breast cancer compared to women in the lowest quartile (p_trend = 0.006). When the association was examined by estrogen‐receptor status, it was only significant for those with estrogen‐receptor‐positive tumors; however, in the competing risk analysis there were no significant differences in the effect estimates by receptor subtype (p_{heterogeneity} = 0.65). Our findings suggest that a dietary pattern associated with higher estrogen levels may increase breast cancer risk. However, whether the influence of this dietary pattern is through a direct effect on estrogen levels deserves further study.     

Dietary folate consumption and risk of ovarian cancer: a prospective cohort study.

Deficient dietary folate intake may be associated with increased cancer risk in humans owing to DNA damage resulting from impaired nucleotide excision repair. It is conceivable that an association with folate may be modified by alcohol and/or methionine intake given that alcohol consumption and low methionine intakes both increase dietary folate requirements. In the cohort study reported here, we examined the association between dietary folate intake and ovarian cancer risk, overall and within strata defined by alcohol and methionine intakes. The investigation was conducted in 49 613 Canadian women who were participants in the National Breast Screening Study and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to cancer and national mortality databases yielded data on cancer incidence and deaths among cohort members, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases among 48 766 women for whom data were available. Dietary folate intake was associated with a 25% decrease in risk of ovarian cancer for the highest versus the lowest quartile level of intake (hazard ratio=0.75, 95% confidence interval=0.42-1.34, Ptrend=0.25). On stratification by alcohol intake, dietary folate was not associated with ovarian cancer risk among women consuming <4 g/day of alcohol, but there was some suggestion of reduced risk at relatively high levels of folate intake among women consuming > or =4 g/day of alcohol/day (Ptrend=0.09; Pinteraction=0.22). The association between folate and ovarian cancer risk did not vary by strata of methionine intake (Pinteraction=0.98). Our findings, while not statistically significant, suggest that relatively high dietary folate intake may be associated with a reduction in ovarian cancer risk among women with relatively high alcohol consumption and among those with relatively high methionine intake.     

Dietary folate intake and pancreatic cancer risk: Results from the European prospective investigation into cancer and nutrition

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/day) compared to the lowest (<241 μg/day) was 0.81 (95% CI: 0.51, 1.31; p_trend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles [HR = 4.42 (95% CI: 1.05, 18.62) for ≥353 μg/day vs. <241 μg/day, p_trend = 0.01]. Nonetheless, there was no significant interaction between smoking and dietary folate intake (p_interaction = 0.99). We found no association between dietary folate intake and PC risk in this large European study.     

Alcohol intake and risk of colorectal cancer: Results from the UK Dietary Cohort Consortium

Background:

Epidemiological studies have suggested that excessive alcohol intake increases colorectal cancer (CRC) risk. However, findings regarding tumour subsites and sex differences have been inconsistent.

Methods:

We investigated the prospective associations between alcohol intake on overall and site- and sex-specific CRC risk. Analyses were conducted on 579 CRC cases and 1996 matched controls nested within the UK Dietary Cohort Consortium using standardised data obtained from food diaries as a main nutritional method and repeated using data from food frequency questionnaire (FFQ).

Results:

Compared with individuals in the lightest category of drinkers (>0–<5 g per day), the multivariable odds ratios of CRC were 1.16 (95% confidence interval (95% CI): 0.88, 1.53) for non-drinkers, 0.91 (95% CI: 0.67, 1.24) for drinkers with 5–<15 g per day, 0.90 (95% CI: 0.65, 1.25) for drinkers with 15–<30 g per day, 1.02 (95% CI: 0.66, 1.58) for drinkers with 30–<45 g per day and 1.19 (95% CI: 0.75, 1.91) for drinkers with ⩾45 g per day. No clear associations were observed between site-specific CRC risk and alcohol intake in either sex. Analyses using FFQ showed similar results.

Conclusion:

We found no significantly increased risk of CRC up to 30 g per day of alcohol intake within the UK Dietary Cohort Consortium.     

Dietary fiber intake and ovarian cancer risk: a prospective cohort study

There is some evidence from case–control studies that dietary fiber intake might be inversely associated with ovarian cancer risk, but there are limited prospective data. Therefore, we examined ovarian cancer risk in association with intake of dietary fiber in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study (NBSS), who completed a self-administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. Data from the food frequency questionnaire were used to estimate intake of total dietary fiber, of fiber fractions, and of fiber from various sources. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between energy-adjusted quartile levels of fiber intake and ovarian cancer risk. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases. Total dietary fiber and fiber fractions were not associated with ovarian cancer risk in this study population.     

Dietary folate and colorectal cancer

Folate may be inversely related to colorectal cancer risk, possibly in combination with low methionine and high alcohol consumption. We considered, therefore, the relation between folate and colorectal cancer in a multicentric case-control study of 1,953 cases and 4,154 controls from Italy, i.e., a population with frequent regular alcohol drinking. In the overall data set, the odds ratio (OR) was 0.72 for the highest quintile of folate, and the continuous OR per 100 microg was 0.86. The inverse relation was similar in men and women and somewhat stronger for the rectum (OR = 0.59 for the highest quintile) compared to the colon (OR = 0.81). It was also somewhat stronger in the highest tertile of alcohol drinking (OR = 0.65), though trends were not heterogeneous across strata of alcohol, whereas no appreciable difference was observed across strata of methionine intake. Compared to subjects reporting low alcohol, high methionine and high folate intake, the OR was 1.83 for those reporting high alcohol, low methionine and low folate intake. The present findings support a favorable role of folate in colorectal carcinogenesis.     

Dietary folate intake and lung cancer risk in former smokers: a case-control analysis.

No studies have focused on the role of dietary folate intake in risk of lung cancer in former smokers, in whom dietary folate intake is less likely confounded with current smoking. Therefore, we evaluated the association between dietary folate intake and risk of lung cancer in a population of 470 histopathologically confirmed incident lung cancer cases from M. D. Anderson Cancer Center and 472 cancer-free controls from enrollees at a community-based multispecialty physician practice, frequency-matched on age (5 years), sex, and ethnicity. Dietary folate intake levels were estimated from a National Cancer Institute standard food frequency questionnaire. Unconditional logistic regression analyses were used to calculate the crude and adjusted ORs and their 95% CIs. Dietary folate intake from natural food was significantly higher among the controls than among the cases (P < 0.001), and folate intake above the control median value was associated with a 40% decreased risk of lung cancer (adjusted OR, 0.60; 95% CI, 0.45-0.79). A significant inverse dose-response relationship between increasing dietary folate and decreasing risk of lung cancer was also evident (adjusted OR, 1.02; 95% CI, 0.71-1.47; OR, 0.67; 95% CI, 0.46-0.99; and OR, 0.53; 95% CI, 0.35-0.80 for the second, third, and fourth quartiles of average folate intake, respectively; P for trend <0.001). A more pronounced inverse association between dietary folate intake and lung cancer risk was observed among subjects who drank alcohol, had smoked relatively more, those who did not take supplemental folate, and those who reported a family history of lung cancer. Our data suggest that there is a possible protective role of dietary folate in lung carcinogenesis, a finding which may have implications in public health and cancer prevention.     

Multivitamin and alcohol intake and folate receptor alpha expression in ovarian cancer.

Folate receptor alpha (FRalpha) expression in epithelial ovarian cancer may be related to folate intake. We examined this association using multivitamin intake, a proxy for folic acid, and assessed whether the relation was modified by alcohol intake, a folate agonist. Cases (n = 148) with suspected epithelial ovarian cancer, of ages > or = 20 years, were seen at Mayo Clinic, Minnesota, between 2000 and 2004; those with tumor specimens (n = 108) were included in analyses. Outpatient controls (n = 148) without cancer and with at least one ovary intact were matched to cases by age (within 5 years) and state of residence. Multivitamin (> or = 4 pills/wk) and weekly alcohol (> or = 5 drinks) intakes were assessed. Tumor specimens were analyzed immunohistochemically for FRalpha. Multivariable rate ratios (RR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. In case-control analysis, the RRs of multivitamin intake with absent/weak/moderate and strong-expressing FRalpha tumors were 0.30 (95% CI, 0.12-0.70) and 0.47 (95% CI, 0.24-0.91), respectively. For alcohol, the associations were 0.84 (95% CI, 0.24-2.86) and 1.65 (95% CI, 0.69-3.93), respectively. In case-case analysis, the RR associated with developing strong-expressing versus other FRalpha tumors was 3.13 (95% CI, 1.14-8.65) for multivitamins and 1.58 (95% CI, 0.45-5.60) for alcohol. The data did not support evidence for an interaction between multivitamin and alcohol intake with risk of developing a strong-expressing FRalpha tumor. The association of multivitamin intake with ovarian cancer may depend on FRalpha expression level.     

Dietary fat intake and risk of epithelial ovarian cancer by tumour histology

Background:

Studies of fat intake and epithelial ovarian cancer (EOC) risk have reported inconsistent findings, hence we hypothesised that associations may vary by histologic subtype.

Methods:

We evaluated fat intake in a New England case–control study including 1872 cases and 1978 population-based controls (1992–2008). Epithelial ovarian cancer risk factors and diet were assessed using a food frequency questionnaire at enrolment. Logistic regression was used to estimate associations between fat intake and EOC risk and polytomous logistic regression was used to test whether associations varied by histologic subtype.

Results:

We observed a decreased risk of EOC when comparing the highest vs lowest quartiles of intake of omega-3 (odds ratio (OR)=0.79, 95% confidence interval (CI) 0.66–0.96, P-trend=0.01) and omega-6 (OR=0.77, 95% CI 0.64–0.94, P-trend=0.02) and an increased risk with high consumption of trans fat (OR=1.30, 95% CI 1.08–1.57, P-trend=0.002). There was no significant heterogeneity by tumour histologic subtype; however, we observed a strong decreased risk for endometrioid invasive tumours with high intake of omega-3 (quartile (Q) 4 vs Q1, OR=0.58, 95% CI 0.41–0.82, P-trend=0.003).

Conclusions:

These findings suggest that higher intake of omega-3 may be protective for EOC overall and endometrioid tumours in particular, whereas greater consumption of trans fat may increase risk of EOC overall.     

Folate intake and stomach cancer incidence in a prospective cohort of Swedish women.

BACKGROUND: Experimental and epidemiologic evidence suggests that folate may play a role in the development of some cancers. Case-control studies and one prospective cohort study on folate intake in relation to stomach cancer risk have yielded inconsistent results. METHODS: We prospectively investigated the relation between folate intake and the incidence of stomach cancer among 61,433 women in the Swedish Mammography Cohort. Participants completed a food frequency questionnaire at baseline (1987-1990) and again in 1997. During follow-up through December 2004, 156 incident stomach cancer cases were diagnosed. Cox proportional hazards models were used to calculate multivariate-adjusted hazard ratios. RESULTS: There was no association between dietary folate intake (i.e., folate from food sources) and the risk of stomach cancer. The multivariate hazard ratio for the highest compared with the lowest category of updated average dietary folate intake was 1.04 (95% confidence interval, 0.61-1.86; P(trend) = 0.91). The relation between dietary folate intake and stomach cancer did not vary significantly by intake of alcohol, methionine, or caffeine. CONCLUSION: Results from this prospective study do not support an association between dietary folate intake and risk of stomach cancer.     

Dietary fat intake and risk of ovarian cancer in the NIH-AARP Diet and Health Study

Background:

Fat intake has been postulated to increase risk of ovarian cancer, but previous studies have reported inconsistent results.

Methods:

The NIH-AARP Diet and Health Study, a large prospective cohort, assessed diet using a food frequency questionnaire at baseline in 1995–1996. During an average of 9 years of follow-up, 695 ovarian cancer cases were ascertained through the state cancer registry database. The relative risks (RRs) and 95% confidence interval (CI) were estimated using a Cox proportional hazard model.

Results:

Women in the highest vs the lowest quintile of total fat intake had a 28% increased risk of ovarian cancer (RR_{Q5 vs Q1}=1.28, 95% CI: 1.01–1.63). Fat intake from animal sources (RR_{Q5 vs Q1}=1.30; 95% CI: 1.02–1.66), but not from plant sources, was positively associated with ovarian cancer risk. Saturated and monounsaturated fat intakes were not related to risk of ovarian cancer, but polyunsaturated fat intake showed a weak positive association. The association between total fat intake and ovarian cancer was stronger in women who were nulliparous or never used oral contraceptives.

Conclusion:

Fat intake, especially from animal sources, was related to an increased risk of ovarian cancer. The association may be modified by parity and oral contraceptive use, which warrants further investigation.     

Dietary cholesterol intake and cancer

BackgroundThis study assesses the association between dietary cholesterol intake and the risk of various cancers.Patients and methodsMailed questionnaires were completed between 1994 and 1997 in eight Canadian provinces by 1182 incident histologically confirmed cases of the stomach, 1727 of the colon, 1447 of the rectum, 628 of the pancreas, 3341 of the lung, 2362 of the breast, 442 of the ovary, 1799 of the prostate, 686 of the testis, 1345 of the kidney, 1029 of the bladder, 1009 of the brain, 1666 non-Hodgkin's lymphomas (NHL), 1069 leukemia and 5039 population controls. Information on dietary habits and nutrition intake were obtained using a food frequency questionnaire, which provided data on eating habits 2 years before the study. Odds ratios (ORs) were derived by unconditional logistic regression to adjust for total energy intake and other potential confounding factors.ResultsDietary cholesterol was positively associated with the risk of cancers of the stomach, colon, rectum, pancreas, lung, breast (mainly postmenopausal), kidney, bladder and NHL: the ORs for the highest versus the lowest quartile ranged from 1.4 to 1.7. In contrast, cholesterol intake was inversely associated with prostate cancer.ConclusionsOur findings add to the evidence that high cholesterol intake is linked to increased risk of various cancers. A diet low in cholesterol may play a role in the prevention of several cancers.     

Dietary fat intake and cancer

International, multidisciplinary biomedical research in the field of nutrition and cancer has led to the recognition that the traditional Western total fat intake of about 40% calories constitutes a major risk factor for cancer of the postmenopausal breast, distal colon, pancreas, ovary, endometrium, and probably prostate. The underlying complex mechanisms have been sketched out, justifying public health promotion activities involving reduction of fat intake to 20 to 25% of calories, facilitated by the deliberate marketing of low-fat products by the food industries.