Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Toenail selenium status and risk of subtypes of head-neck cancer: The Netherlands Cohort Study.

BACKGROUND: There is limited prospective data on the relationship between selenium status and the risk of head-neck cancer (HNC) and HNC subtypes (i.e., oral cavity cancer [OCC], oro-/hypopharyngeal cancer [OHPC] and laryngeal cancer [LC]). Therefore, we investigated the association between toenail selenium, reflecting long-term selenium exposure, and HNC risk within the Netherlands Cohort Study. METHODS: At baseline, 120,852 participants completed a self-administered questionnaire about diet and other cancer risk factors and were asked to provide toenail clippings. After 20.3 years of follow-up, 294 cases of HNC (95 OCC, 62 OHPC, two oral cavity/pharynx unspecified or overlapping and 135 LC) and 2,164 subcohort members were available for case-cohort analysis using Cox proportional hazards models. RESULTS: Toenail selenium status was statistically significantly associated with a decreased risk of HNC overall (multivariate RR for quartile four versus one: 0.55, 95% confidence interval [CI] 0.37-0.82, P trend = 0.001). The association between toenail selenium and risk of HNC overall was stronger among men than women, but no statistically significant interaction with sex was found. Toenail selenium level was also associated with a decreased risk of all HNC subtypes, with statistically significant associations in OHPC and LC. No statistically significant interaction was found between toenail selenium level and cigarette smoking or alcohol consumption for HNC overall. CONCLUSIONS: In this large cohort study, we found an inverse association between toenail selenium level and HNC risk. Among HNC subtypes, this association was strongest for OHPC and LC. Furthermore, the association of toenail selenium status with HNC risk was stronger among men than women.

Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies.

BACKGROUND: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. RESULTS: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. CONCLUSIONS: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.

Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies.

PURPOSE: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. METHODS: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model. RESULTS: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95% confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95% CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types. CONCLUSION: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.

Vitamin and carotenoid intake and risk of head-neck cancer subtypes in the Netherlands Cohort Study.

BACKGROUND: Head and neck cancer (HNC) is the seventh most-common type of cancer worldwide. Evidence regarding the potential protective effect of vitamins and carotenoids on HNC is limited and mostly based on case-control studies. OBJECTIVE: We evaluated the association of intake of dietary vitamins C and E (including supplementation) and the most-common carotenoids (α-carotene, ß-carotene, lutein plus zeaxanthin, lycopene, and ß-cryptoxanthin) and risk of HNC and HNC subtypes in a large prospective study. DESIGN: The Netherlands Cohort Study included 120,852 participants. For efficiency reasons, a case-cohort design was used. At baseline in 1986, participants completed a food-frequency questionnaire. A subcohort was randomly selected from the total cohort. After 20.3 y of follow-up, 3898 subcohort members and 415 HNC cases [131 oral cavity cancer (OCCs), 88 oro-/hypopharyngeal cancer (OHPs), and 193 laryngeal cancer cases] were available for analysis. Rate ratios and 95% CIs for highest (quartile 4) compared with lowest (quartile 1) quartiles of vitamin and carotenoid intake were estimated by using the Cox proportional hazards model. RESULTS: A strong inverse association was shown between vitamin C and HNC overall (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.39; 95% CI: 0.23, 0.66; P-trend < 0.001), OCC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.35; 95% CI: 0.16, 0.77; P-trend < 0.05), and OHPC (multivariable-adjusted rate ratio for quartile 4 compared with quartile 1: 0.29; 95% CI: 0.12, 0.67; P-trend < 0.01). No statistically significant results were shown for vitamin E, α-carotene, ß-carotene, lycopene, and lutein plus zeaxanthin. The association of vitamin E and HNC was modified by alcohol status (P-interaction = 0.003) with lower risks in alcohol abstainers. CONCLUSIONS: With this study, we show an inverse association between intake of vitamin C and the incidence of HNC and HNC-subtypes. Future research is recommended to investigate the underlying mechanisms and to confirm our results, which may be promising for the prevention of HNC.

Selenoprotein gene variants, toenail selenium levels, and risk for advanced prostate cancer.

Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case-cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; P trend = .01), GPX1 rs17650792 (higher risk; P trend = .03), and GPX1 rs1800668 (lower risk; P trend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.

Cancer incidence in Dutch Balkan veterans.

Suspicion has been raised about an increased cancer risk among Balkan veterans because of alleged exposure to depleted uranium. The authors conducted a historical cohort study to examine cancer incidence among Dutch Balkan veterans. Male military personnel (n=18,175, median follow-up 11 years) of the Army and Military Police who had been deployed to the Balkan region (1993-2001) was compared with their peers not deployed to the Balkans (n=135,355, median follow-up 15 years) and with the general Dutch population of comparable age and sex. The incidence of all cancers and 4 main cancer subgroups was studied in the period 1993-2008. The cancer incidence rate among Balkan deployed military men was 17% lower than among non-Balkan deployed military men (hazard ratio 0.83 (95% confidence interval 0.69, 1.00)). For the 4 main cancer subgroups, hazard ratios were statistically non-significantly below 1. Also compared to the general population cancer rates were lower in Balkan deployed personnel (standardised incidence rate ratio (SIR) 0.85 (0.73, 0.99). The SIR for leukaemia was 0.63 (0.20, 1.46). The authors conclude that earlier suggestions of increased cancer risks among veterans are not supported by empirical data. The lower risk of cancer might be explained by the 'healthy warrior effect'.

Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis.

BACKGROUND: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). OBJECTIVE: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. DESIGN: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. RESULTS: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% CI: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. CONCLUSION: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer.

Consumption of dietary fat and meat and risk of ovarian cancer in the Netherlands Cohort Study.

BACKGROUND: Evidence that links dietary factors to ovarian cancer is conflicting, but several epidemiologic studies suggested that consumption of dietary fat and meat may increase risk of ovarian cancer. OBJECTIVE: We studied associations of intakes of total fat and sources and subtypes of fat, fresh meat, processed meat, and fish with ovarian cancer risk within the Netherlands Cohort Study (NLCS). DESIGN: The NLCS includes 62,573 postmenopausal women, aged 55-69 y at baseline, who completed a baseline questionnaire on dietary habits and other risk factors for cancer in 1986. After 16.3 y of follow-up, 340 ovarian cancer cases and 2161 subcohort members were available for a case-cohort analysis. Multivariable rate ratios (RRs) were adjusted for age at baseline, total energy intake, oral contraceptive use, and parity. RESULTS: There were no clear associations between intakes of total fat, saturated fat, mono- and polyunsaturated fats, animal fat, plant-based fat, dairy fat, other fat sources, fresh meat, processed meat, and fish and ovarian cancer risk. There was a positive association between consumption of trans unsaturated fatty acids and ovarian cancer risk. The multivariable RR for women in the highest compared with the lowest quintiles of intake was 1.51 (95% CI: 1.04, 2.20; P for trend = 0.01). Although no significant interactions by oral contraceptive use or parity were shown, effect sizes were generally more pronounced and significant in women who never used oral contraceptives and in parous women. CONCLUSION: This prospective study suggests that trans unsaturated fatty acids, but no other types of fat or meat, are associated with increased ovarian cancer risk.

Toenail selenium status and the risk of Barrett's esophagus: the Netherlands Cohort Study.

OBJECTIVE: To investigate the association between selenium and the risk of Barrett's esophagus (BE), the precursor lesion of esophageal adenocarcinoma. METHODS: Data from the prospective Netherlands Cohort Study were used. This cohort study was initiated in 1986, when 120,852 subjects aged 55-69 years completed a questionnaire on dietary habits and lifestyle, and provided toenail clippings for the determination of baseline selenium status. After 16.3 years of follow-up, 253 BE cases (identified through linkage with the nationwide Dutch pathology registry) and 2,039 subcohort members were available for case-cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR). RESULTS: The multivariable-adjusted RR for the highest versus the lowest quartile of toenail selenium was 1.06 (95% CI 0.71-1.57). No dose-response trend was seen (p trend = 0.99). No association was found in subgroups defined by sex, smoking status, body mass index (BMI), or intake of antioxidants. For BE cases that later progressed to high-grade dysplasia or adenocarcinoma, the RR for a selenium level above the median vs. below the median was 0.64 (95% CI 0.24-1.76). CONCLUSIONS: In this large prospective cohort study, we found no evidence of an association between selenium and risk of BE.

Fluid intake and colorectal cancer risk in the Netherlands Cohort Study.

Total fluid intake, specifically water intake, has been suggested to protect against colorectal cancer. We examined the association of total fluid intake with colorectal cancer endpoints and possible effect modification by fiber intake within the Netherlands Cohort Study (N = 120,852). We also investigated intake of specific beverages. After 13.3 yr, 1,443 male and 1,040 female colorectal cancer cases with complete baseline questionnaires were available for case-cohort analyses. Multivariate analyses showed no dose-response relationship of total fluid intake and intake of specific beverages with the risk of overall colorectal, proximal, and distal colon cancer. For rectal cancer risk in men, there was a nonsignificant positive trend for total fluid intake [> 1,500 vs. 6 vs.

Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study.

BACKGROUND & AIMS: Selenium may protect against the development of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric cardia adenocarcinoma (GCA). Only in very few studies have the associations with ESCC and GCA been investigated, and no epidemiologic studies exist on EAC. METHODS: We studied the association between selenium and risk of ESCC, EAC, and GCA within the prospective Netherlands Cohort Study, conducted among 120,852 men and women aged 55-69 years at baseline. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 16.3 years of follow-up, 64 ESCC, 112 EAC, and 114 GCA cases and 2072 subcohort members were available for case-cohort analysis. Incidence rate ratios (RR) were calculated using Cox proportional hazards models. RESULTS: In multivariable analyses of selenium status, we found an inverse association with ESCC (RR(per standard unit increment), 0.80; 95% confidence interval [CI]: 0.67-0.96) and a borderline significant inverse association with GCA (RR, 0.91; 95% CI: 0.80-1.02). No overall association was observed for EAC (RR, 1.05; 95% CI: 0.95-1.15), but, for women and never smokers, significant inverse associations were found (RR(per standard unit increment), 0.72; 95% CI: 0.61-0.84 and RR(per standard unit increment), 0.74; 95% CI: 0.64-0.86, respectively). CONCLUSIONS: This prospective study supports an inverse association between toenail selenium and risk of ESCC and GCA and suggests an inverse association with risk of EAC in subgroups (women, never smokers, and low antioxidant consumers). These associations need confirmation.

Carotenoid and vitamin intake, von Hippel-Lindau gene mutations and sporadic renal cell carcinoma.

OBJECTIVE: We investigated whether dietary carotenoid and vitamin intake and supplemental vitamin use were inversely associated with RCC risk and with Von Hippel-Lindau (VHL)-gene mutations in clear-cell renal cell carcinoma (RCC). METHODS: The Netherlands Cohort Study on diet and cancer (NLCS) includes 120,852 persons, who completed a self-administered food-frequency questionnaire in 1986. After 11.3 years of follow-up, 284 cases and a random sample of 4,095 persons (subcohort) with complete data were included in multivariable analyses using a case-cohort approach. VHL gene mutational analysis was complete for 225 cases. Rate ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard models, while adjusting for age, sex, smoking, body mass index, and a history of hypertension. RESULTS: We observed no association for dietary carotenoid and vitamin intake and RCC risk, and a somewhat increased risk with supplemental vitamin E, AD, and multivitamin use. Results were suggestive of higher RRs for alpha-carotene, beta-cryptoxanthin, folate, and supplemental vitamin C and multivitamin intake for wildtype VHL tumors compared to VHL-mutated tumors. CONCLUSIONS: There was no association of carotenoid, vitamin or supplemental vitamin intake and RCC risk. These associations should be investigated by others to confirm the current observations.

Intakes of coffee, tea, milk, soda and juice and renal cell cancer in a pooled analysis of 13 prospective studies.

Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; pvalue, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer. (c) 2007 Wiley-Liss, Inc.