[Show abstract][Hide abstract] ABSTRACT: Background: Increased oxidative stress has been linked to prostate cancer (PrCa). We investigated oxidative stress-related genetic variants in relation to advanced PrCa risk and examined potential interactions with pro- and antioxidant exposures. Methods: A case-cohort analysis was conducted in the prospective Netherlands Cohort Study, which included 58,279 men aged 55-69 years. Cohort members completed a baseline questionnaire and provided toenail clippings, which were used to isolate DNA. Advanced PrCa cases were identified during 17.3 years of follow-up. The analysis included 14 genetic variants and 11 exposures. Cox regression models were used for analysis and false discovery rate (FDR) Q-values were calculated. Results: Complete genotyping data were available for 952 cases and 1,798 subcohort members. CAT rs1001179 was associated with stage III/IV and stage IV PrCa risk, with HRs per minor allele of 1.16 (95% CI: 1.01-1.33; P=0.032) and 1.25 (95% CI: 1.07-1.46; P=0.006), respectively. We tested 151 gene-environment interactions in relation to both stage III/IV and IV PrCa risk. Seven interactions were statistically significant after adjusting for multiple testing (FDR Q-value <0.20); for stage III/IV PrCa these involved intake of β-carotene (GPX1 rs17650792, hOGG1 rs1052133) and heme iron (GPX1 rs1800668 and rs3448), and for stage IV PrCa these involved intake of catechin (SOD2 rs4880) and heme iron (hOGG1 rs1052133, SOD1 rs10432782). Conclusion: This study of advanced PrCa risk showed a marginal association with a CAT polymorphism and seven novel gene-environment interactions in the oxidative stress pathway. Impact: Oxidative stress-related genes and exposures may have a joint effect on advanced PrCa.
[Show abstract][Hide abstract] ABSTRACT: Background: Previous epidemiologic research suggests a protective role of one-carbon nutrients in carcinogenesis. Folate, however, may play a dual role in neoplasms development: protect early in carcinogenesis, promote carcinogenesis at a later stage. We prospectively examined associations between intake of total folate, methionine, riboflavin, vitamin B6 and risk of lymphoid and myeloid neoplasms (including subtypes) and investigated whether alcohol modified the effects of folate. Methods: The Netherlands Cohort Study consists of 120,852 individuals who completed a baseline questionnaire in 1986, including a 150-item food-frequency questionnaire. After 17.3 years of follow-up, 1,280 cases of lymphoid and 222 cases of myeloid neoplasms were available for analysis. Results: Intakes of folate, methionine, and riboflavin were not associated with lymphoid or myeloid neoplasms. For vitamin B6, a statistically significantly increased myeloid neoplasms risk was observed (highest versus lowest quintile: HR=1.87, 95%CI=1.08-3.25). When analyzing by lymphoid and myeloid neoplasms subtypes, no clear associations were observed for most subtypes, with just a few increased risks for some subtypes and nutrients. Some risks became non-significant after excluding early cases. No interaction between alcohol and folate was observed. Conclusions: We observed a few significant positive associations; however, some of these would be expected to arise due to chance alone. Furthermore, some risks became non-significant after excluding early cases. Therefore, we conclude that there is no association between one-carbon nutrient intake and risk of lymphoid and myeloid neoplasms. Impact: This study contributes substantially to the limited and inconclusive evidence on the association with one-carbon nutrients.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of the National Cancer Institute 02/2014; 106(3). DOI:10.1093/jnci/dju003 · 12.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
To date, only a few risk factors for pancreatic cancer have been established. We examined prospectively relations between several medical conditions and pancreatic cancer incidence.
In 1986, 120 852 participants completed a baseline questionnaire on cancer risk factors, including several self-reported physician diagnosed medical conditions. At baseline, a random subcohort of 5000 participants was selected using a case-cohort approach for analysis. After 16.3 years of follow-up, 448 pancreatic cancer cases (63% microscopically confirmed) were available for analysis.
Diabetes mellitus type II and hepatitis were positively associated with pancreatic cancer risk (multivariable-adjusted hazard ratio: 1.79; 95% confidence interval: 1.12–2.87 and hazard ratio: 1.37; 95% confidence interval: 1.04–1.81, respectively). Furthermore, a positive trend in risk with increasing years of diagnosis of diabetes (P=0.004) and of hepatitis (P=0.02) was observed. However, an inverse association was observed between hypertension and pancreatic cancer risk, this was found among microscopically confirmed cases only (hazard ratio: 0.66; 95% confidence interval: 0.49–0.90), while years since diagnosis of hypertension significantly decreased cancer risk (P for trend=0.02).
In this prospective study, a positive association was observed between self-reported physician diagnosed diabetes mellitus type II and hepatitis and pancreatic cancer risk, whereas an inverse association was observed with hypertension.
British Journal of Cancer 10/2013; 109(11). DOI:10.1038/bjc.2013.629 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
Toenail selenium was associated with a substantial decrease in risk of advanced PCa.
JNCI Journal of the National Cancer Institute 07/2013; DOI:10.1093/jnci/djt186 · 12.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American journal of epidemiology 05/2013; 177(12). DOI:10.1093/aje/kws419 · 5.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Our results do not support an association of dietary folate or specific folate vitamers on the risk of prostate cancer, or advanced prostate cancer.
Cancer Causes and Control 10/2012; 23(12). DOI:10.1007/s10552-012-0079-7 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Oxidative stress is possibly related to prostate carcinogenesis. We constructed a dietary antioxidant score, which is a measure of combined antioxidant exposures, and an oxidative balance score (OBS), which is a measure of combined antioxidant and pro-oxidant exposures. We hypothesized that both scores are inversely associated with the risk of prostate cancer (PCa).
We conducted a case-cohort study among 58,279 men in the Netherlands Cohort Study. Cohort members completed a baseline questionnaire. From 1986 to 2003, 3451 patients with PCa were identified including 1196 advanced cancers (stage III/IV). The antioxidant score and the OBS were created by summing quartile and category scores of individual score constituents, which had an equal weight. Pro-oxidants were scored in the opposite way to antioxidants.
Both the antioxidant score and OBS were not associated with risk of overall PCa or PCa subgroups on the basis of disease stage. Most score constituents were not associated with the risk of PCa. Total catechin intake was associated with a decreased risk of stage IV PCa (greatest vs. lowest quartile: hazard ratio, 0.76; 95% confidence interval, 0.59-0.98).
The antioxidant score and OBS were not associated with risk of overall and advanced-stage PCa.
Annals of epidemiology 09/2012; 22(11). DOI:10.1016/j.annepidem.2012.07.010 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Cancer 01/2012; 130(1):147-58. DOI:10.1002/ijc.25989 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiologic studies of pancreatic cancer risk have reported null or nonsignificant positive associations for obesity, while associations for height have been null. Waist and hip circumference have been evaluated infrequently. A pooled analysis of 14 cohort studies on 846,340 individuals was conducted; 2,135 individuals were diagnosed with pancreatic cancer during follow-up. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Compared to individuals with a body mass index (BMI) at baseline between 21-22.9 kg/m(2) , pancreatic cancer risk was 47% higher (95%CI:23-75%) among obese (BMI ≥ 30 kg/m(2) ) individuals. A positive association was observed for BMI in early adulthood (pooled multivariate [MV]RR = 1.30, 95%CI = 1.09-1.56 comparing BMI ≥ 25 kg/m(2) to a BMI between 21 and 22.9 kg/m(2) ). Compared to individuals who were not overweight in early adulthood (BMI < 25 kg/m(2) ) and not obese at baseline (BMI < 30 kg/m(2) ), pancreatic cancer risk was 54% higher (95%CI = 24-93%) for those who were overweight in early adulthood and obese at baseline. We observed a 40% higher risk among individuals who had gained BMI ≥ 10 kg/m(2) between BMI at baseline and younger ages compared to individuals whose BMI remained stable. Results were either similar or slightly stronger among never smokers. A positive association was observed between waist to hip ratio (WHR) and pancreatic cancer risk (pooled MVRR = 1.35 comparing the highest versus lowest quartile, 95%CI = 1.03-1.78). BMI and WHR were positively associated with pancreatic cancer risk. Maintaining normal body weight may offer a feasible approach to reducing morbidity and mortality from pancreatic cancer.
International Journal of Cancer 10/2011; 129(7):1708-17. DOI:10.1002/ijc.25794 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer.
We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer risk.
The Netherlands Cohort Study consisted of 120,852 individuals who completed a baseline questionnaire in 1986. After 13.3 y of follow-up, 408 cases were available for analysis. Self-reported information on physical activity was collected. Three indicators were used as proxies for energy restriction: father's employment status during the Economic Depression (1932-1940) and place of residence during the World War II years (1940-1944) and the Hunger winter (1944-1945).
For past sports activities, we observed a significantly decreased risk of pancreatic cancer (HR: 0.80; 95% CI: 0.64, 0.99). Proxies for energy restriction were not related to pancreatic cancer risk. When the results for energy restriction were stratified by height, a significant multiplicative interaction was observed for the Economic Depression period (P = 0.002). Shorter individuals (height less than the sex-specific median adult height) with an unemployed father during the Economic Depression period had a significantly lower cancer risk (HR: 0.31; 95% CI: 0.14, 0.66) than did taller individuals with an employed father. No significant interactions were observed for exposure to energy restriction during the World War II years and the Hunger winter.
Our results suggest a modestly decreased risk of pancreatic cancer associated with past sports activity. With respect to proxies for energy restriction, our findings suggest that shorter individuals exposed to energy restriction during adolescence may have a reduced risk, whereas taller individuals may not.
American Journal of Clinical Nutrition 09/2011; 94(5):1314-23. DOI:10.3945/ajcn.110.007542 · 6.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To date, cigarette smoking is the most consistent risk factor for pancreatic cancer. We prospectively examined the role of active cigarette smoking, smoking cessation, and passive smoking as determinants for pancreatic cancer.
The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 16.3 years of follow-up, 520 incident pancreatic cancer cases were available for analysis. A case-cohort approach was employed using the person-years of follow-up of a random subcohort (n = 5,000), which was chosen immediately after baseline.
Compared with never cigarette smokers, both former and current cigarette smokers had an increased pancreatic cancer risk [multivariable-adjusted hazard rate ratio (HR), 1.34; 95% confidence interval (CI), 1.02-1.75 and HR, 1.82; 95% CI, 1.40-2.38, respectively]. We observed an increased pancreatic cancer risk per increment of 10 years of smoking (HR, 1.15; 95% CI, 1.08-1.22) and an HR of 1.08 per increment of 10 cigarettes/d (95% CI, 0.98-1.19). Quitting smoking gradually reduced pancreatic cancer risk and approached unity after > or = 20 years of quitting. No association was observed for passive smoking exposure and pancreatic cancer risk in women; in men, this association was not investigated because >90% of the men were ever smokers.
Overall, our findings confirmed that cigarette smoking is an important risk factor for pancreatic cancer, whereas quitting smoking reduced risk. No association was observed between passive smoking exposure and pancreatic cancer risk in women.
Quitting smoking would benefit the burden on pancreatic cancer incidence.