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.

Advanced prostate cancer risk in relation to toenail selenium levels.

BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from the Netherlands where low selenium status is widespread. METHODS: The analysis was conducted in the prospective Netherlands Cohort Study, which included 58 279 men aged 55 to 69 years at baseline in 1986. All cohort members completed a baseline questionnaire, and approximately 79% of participants provided toenail clippings, which were used for toenail selenium measurements using instrumental neutron activation analysis. Incident advanced PCa case subjects from the entire cohort were identified during 17.3 years of follow-up. The study employed a case-cohort design for which a random subcohort was sampled at baseline. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. All tests were two-sided. RESULTS: Complete toenail selenium data were available for 898 advanced (International Union Against Cancer stage III/IV) PCa case subjects and 1176 subcohort members. The average toenail selenium concentration of subcohort members was 0.550 µg/g. Toenail selenium was associated with a reduced risk of advanced PCa; adjusted hazard ratio for the highest vs lowest quintile was 0.37 (95% CI = 0.27 to 0.51; P trend < .001). For stage IV PCa, men in the highest vs lowest quintile of toenail selenium had an adjusted hazard ratio of 0.30 (95% CI = 0.21 to 0.45; P trend < .001). CONCLUSIONS: Toenail selenium was associated with a substantial decrease in risk of advanced PCa.

Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer.

Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

Intake of vegetables, fruits, carotenoids and vitamins C and E and pancreatic cancer risk in The Netherlands Cohort Study.

Epidemiological data investigating the relation between fruit and vegetable consumption and pancreatic cancer risk have shown inconsistent results so far. Most case-control studies observed an inverse association with total fruit and vegetable consumption, whereas results from most cohort studies have largely been null. We examined prospectively the relation between pancreatic cancer risk and intake of vegetables, fruits, carotenoids and vitamins C and E. The Netherlands Cohort Study consisted of 120,852 men and women who completed a questionnaire at baseline in 1986, including a validated 150-item food-frequency questionnaire. After 16.3 years of follow-up, 423 cases were available for analysis. Total vegetable and total fruit consumption were not associated with pancreatic cancer risk (highest vs. lowest quintile, multivariable-adjusted hazard rate ratio = 1.23, 95% confidence interval: 0.86-1.75 and multivariable-adjusted hazard rate ratio = 0.90, 95% confidence interval: 0.66-1.24, respectively). Also, for cooked vegetables, raw vegetables and vegetables and fruits classified into subgroups, no associations were observed. Dietary carotenoids, vitamin C and E intake and supplements containing vitamin C or E were not associated with pancreatic cancer risk. The results were not modified by sex, smoking status and body mass index. In conclusion, we observed no association between a high consumption of vegetables and fruits and pancreatic cancer risk in this large cohort study, which is in agreement with previous prospective studies. Furthermore, we observed no association between the intake of carotenoids, vitamins and vitamin supplements and pancreatic cancer risk.

Dietary folate and folate vitamers and the risk of pancreatic cancer in the Netherlands cohort study.

An association between high intake of folate and reduced risk of cancer has been suggested by previous research. However, epidemiologic data from cohort studies regarding the relationship between dietary folate and pancreatic cancer are sparse and inconsistent. We examined the association between dietary folate intake and risk of pancreatic cancer within the Netherlands Cohort Study on diet and cancer. Men and women (120,852), ages 55 to 69 years, were recruited. Information on diet was collected at baseline by means of food frequency questionnaires, and the cohort was followed for 13.3 years. Total folate and vitamer intake were calculated using folate contents of food items derived from a validated liquid chromatography trienzyme method. Cases (n = 363) were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. A case-cohort approach was used using the follow-up data of a random subcohort (n = 5,000) identified at the onset of the cohort. Multivariable hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards model. After adjusting for age, gender, smoking status, number of years smoked, number of cigarettes smoked per day, and intake of added sugar multivariate hazard ratio comparing the highest and lowest quintiles of folate intake for pancreatic cancer risk was 1.37 (confidence interval, 0.97-1.94; P(trend) = 0.07). When folate vitamers were analyzed separately, results did not show a difference in association. Our results do not support a protective association of total dietary folate or individual folate vitamers on the risk of pancreatic cancer.