[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: Background: We investigated body size, physical activity, and early life energy restriction in relation to colorectal tumors with and without methylated insulin-like growth factor binding protein (IGFBP) genes, which are putative tumor suppressor genes. Methods: We determined IGFBP2, IGFBP3, and IGFBP7 promoter CpG island hypermethylation in tumors of 733 CRC cases from the Netherlands Cohort Study (N=120,852). Participants self-reported lifestyle and dietary factors at baseline in 1986. Using a case-cohort approach (N subcohort=5,000), we estimated hazard ratios for CRC by extent of IGFBP methylation. Results: Comparison of the highest versus lowest sex-specific tertiles of adult body mass index (BMI) gave multivariable-adjusted hazard ratios (95% confidence intervals (CIs)) for CRCs with 0 (18.7%), 1 (29.5%), 2 (32.4%), and 3 (19.5%) methylated genes of 1.39 (0.88, 2.19), 1.11 (0.77, 1.62), 1.67 (1.17, 2.38), and 2.07 (1.29, 3.33), respectively. Other anthropometric measures and physical activity were not associated with CRC risk by extent of IGFBP methylation, except height in sex-specific analyses for women. Exposure to energy restriction during the Dutch Hunger Winter versus non-exposure gave HRs (95% CIs) for CRCs with 0, 1, 2, and 3 methylated genes of 1.01 (0.67, 1.53), 1.03 (0.74, 1.44), 0.72 (0.52, 0.99), and 0.50 (0.32, 0.78), respectively. Conclusions: Adult BMI, height (in women only), and early life energy restriction were associated with the risk of having a colorectal tumor characterized by IGFBP methylation. Impact: Body size predicts preferentially for IGFBP gene methylated colorectal tumors, which might facilitate more targeted approaches to prevent obesity-related colorectal cancers.
[Show abstract][Hide abstract] ABSTRACT: The evidence for an association between occupational asbestos exposure and pharyngeal cancer (PhC) is limited, while for oral cavity cancer (OCC) the literature is even sparser. We studied OCC and PhC risk both separately and combined (OCPC) in relation to occupational asbestos exposure, specifically addressing the influence of potential confounders, the existence of an exposure-response relation, and the presence of interaction between asbestos and smoking.
Using the prospective Netherlands Cohort Study (N=58 279 men, aged 55-69 years), we estimated asbestos exposure by linkage to a general population job-exposure matrix (DOMJEM) and a Finnish job exposure matrix (FINJEM). After 17.3 years of follow-up, 58 OCC and 53 PhC cases were available for analysis.
No association between asbestos and risk of OCC was observed for either JEM. Hazard ratios (HR) of PhC and OCPC increased after adjusting for confounders, particularly alcohol consumption and socioeconomic status. For PhC, a multivariable-adjusted increased HR was observed for "ever" versus "never" exposed to asbestos [HR 2.20, 95% confidence interval (95% CI) 1.08-4.49] when using FINJEM, but a trend of increased risks with higher cumulative exposure could not be demonstrated for either JEM. Results for OCPC showed patterns similar to those observed for PhC. None of the cancers showed a significant interaction between asbestos and smoking.
This prospective population-based study showed no convincing evidence of an association between asbestos and risk of OCC, PhC, and OCPC as an exposure-response relation was lacking, and results were not robust against the use of different JEM. However, the potentially increased HR of PhC and OCPC observed in this and previous studies warrant further research.
Scandinavian Journal of Work, Environment & Health 05/2014; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Improved prognostic stratification of patients with TNM stage II colorectal cancer is desired, since 20-30% of high-risk stage II patients may die within five years of diagnosis. This study was conducted to investigate REarranged during Transfection (RET) gene promoter CpG island methylation as a possible prognostic marker for TNM stage II colorectal cancer patients (CRC) patients.
The utility of RET promoter CpG island methylation in tumors of stage II CRC patients as a prognostic biomarker for CRC related death was studied in three independent series (including 233, 231, and 294 TNM stage II patients, respectively) by using MSP and pyrosequencing. The prognostic value of RET promoter CpG island methylation was analyzed by using Cox regression analysis.
In the first series, analyzed by MSP, CRC stage II patients (n=233) with RET methylated tumors, had a significantly worse overall survival as compared to those with unmethylated tumors (HRmultivariable = 2.51, 95%-CI: 1.42-4.43). Despite a significant prognostic effect of RET methylation in stage III patients of a second series, analyzed by MSP, the prognostic effect in stage II patients (n=231) was not statistically significant (HRmultivariable = 1.16, 95%-CI 0.71-1.92). The third series (n=294), analyzed by pyrosequencing, confirmed a statistically significant association between RET methylation and poor overall survival in stage II patients (HRmultivariable = 1.91, 95%-CI: 1.03-3.52). Our results show that RET promoter CpG island methylation, analyzed by two different techniques, is associated with a poor prognosis in stage II CRC in two independent series and a poor prognosis in stage III CRC in one series. RET methylation may serve as a useful and robust tool for clinical practice to identify high-risk stage II CRC patients with a poor prognosis. This merits further investigation.
[Show abstract][Hide abstract] ABSTRACT: Prospective data on alcohol consumption, cigarette smoking and risk of head-neck cancer (HNC) subtypes, i.e. oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), are limited. We investigated these associations within the second largest prospective study on this topic so far, the Netherlands Cohort Study.
120,852 participants completed a questionnaire on diet and other cancer risk factors in 1986. After 17.3 years of follow-up, 395 HNC (110 OCC, 83 OHPC, and 199 LC) cases and 4288 subcohort members were available for case-cohort analysis using Cox proportional hazards models.
For total HNC, the multivariable adjusted incidence rate ratio (RR) was 2.74 (95% confidence interval (CI) 1.85-4.06) for those drinking >=30g ethanol/day compared with abstainers; in subtypes, RRs were 6.39 for OCC, 3.52 for OHPC, and 1.54 for LC. Compared with never cigarette smokers, current cigarette smokers had a RR of 4.49 (95%CI 3.11-6.48) for HNC overall, and 2.11 for OCC, 8.53 for OHPC, and 8.07 for LC. A significant, positive, multiplicative interaction between categories of alcohol consumption and cigarette smoking was found for HNC overall (P interaction 0.03).
Alcohol consumption and cigarette smoking were independently associated with risk of HNC overall, with a positive, multiplicative interaction. The strength of these associations differed among HNC-subtypes: OCC was most strongly associated with alcohol consumption but most weakly with cigarette smoking, whereas LC was not statistically significantly associated with alcohol consumption.
BMC Cancer 03/2014; 14(1):187. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.
[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.
[Show abstract][Hide abstract] ABSTRACT: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.
Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86).
Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.
[Show abstract][Hide abstract] ABSTRACT: Acrylamide, a probable human carcinogen, is present in heat-treated carbohydrate-rich foods. Epidemiological studies have not shown a clear association between acrylamide intake and colorectal cancer risk. This may be due to the molecular heterogeneity in colorectal tumors, which was not taken into consideration before. Since the acrylamide metabolite glycidamide induces specific DNA mutations in rodents, we investigated whether acrylamide is associated with colorectal cancer risk characterized by mutations in KRAS and APC; key genes in colorectal carcinogenesis. This case-cohort analysis, within the Netherlands Cohort Study on diet and cancer, was based on 7.3 years of follow-up. Acrylamide intake was assessed with a food frequency questionnaire. Mutation analysis of codons 1286-1520 in exon 15 in APC and codons 12 and 13 in exon 1 in KRAS was performed on tumor tissue of 733 cases. Hazard ratios were calculated using Cox proportional hazards analysis. Among men, acrylamide intake was statistically significantly associated with an increased risk of particularly tumors with an activating KRAS mutation (HR 4(th) quartile vs. 1(st): 2.12 (95% CI: 1.16-3.87), p-trend: 0.01). Among women, acrylamide intake was statistically significantly associated with a decreased risk of particularly tumors with a truncating APC mutation (4(th) quartile vs. 1(st): 0.47 (95% CI: 0.23-0.94), p-trend: 0.02), but only in the highest quartile of intake. This is the first study to show that acrylamide might be associated with colorectal cancer with specific somatic mutations, differentially in men and women. More research is needed to corroborate or refute these findings.
[Show abstract][Hide abstract] ABSTRACT: To calculate the proportion of cancer cases in the Netherlands in 2010 that were attributable to lifestyle factors by using the most recent data.
Lifestyle risk factors studied were tobacco smoking, alcohol consumption, overweight, lack of physical exercise, and six elements of diet (consumption of vegetables, fruit, processed meat and red meat, and calcium and fibre intake). The lifestyle factors were organised so that the group with the highest risk (e.g. smokers) could be compared with the groups with the lowest risk (e.g. ex-smokers, non-smokers). Cut-off points were in line with Dutch public health messages. We obtained prevalence data on risk factors from national databases. Relative risks for the relationship between lifestyle and cancer were based on the international literature. Incidence and mortality data for cancer in 2010 were obtained through the Netherlands Cancer Registry. We calculated percentages of new cancer cases and deaths for men and women and for each type of cancer individually; these were then summed.
We estimated that of the 98,971 newly-diagnosed cases of cancer among persons aged ≥ 20 years in the Netherlands in 2010, 29,938 (30%) were attributable to the above-mentioned lifestyle factors. Smoking was the most important contributory risk factor (19% of all new cancer cases), followed by sub-optimal dietary habits (10%), overweight (4%), alcohol consumption (3%), and lack of physical activity (2%). Of cancer deaths in 2010, an estimated 38% were attributable to lifestyle factors. Projections for 2020 show that lack of exercise and consumption of alcohol and meat will contribute less to the development of cancer while overweight and a reduction in inadequate dietary fibre intake and inadequate fruit and vegetable consumption will contribute more.
Almost one-third of all cases of cancer and almost 40% of deaths from cancer can be attributed to a less healthy lifestyle.
Nederlands tijdschrift voor geneeskunde 01/2014; 159:A8085.
[Show abstract][Hide abstract] ABSTRACT: Background
Metabolomics, defined as the comprehensive identification and quantification of low-molecular-weight metabolites to be found in a biological sample, has been put forward as a potential tool for classifying individuals according to their risk of coronary heart disease (CHD). Here, we investigated whether a single-point blood measurement of the metabolome is associated with and predictive for the risk of CHD.
Methods & Results
We obtained proton nuclear magnetic resonance (1H-NMR) spectra in 79 cases who developed CHD during follow-up (median 8.1 years) and in 565 randomly selected individuals. In these spectra 100 signals representing 36 metabolites were identified. Applying LASSO regression, we defined a weighted metabolite score consisting of 13 1H-NMR signals that optimally predicted CHD. This metabolite score, including signals representing a lipid fraction, glucose, valine, ornithine, glutamate, creatinine, glycoproteins, citrate and 1.5-anhydrosorbitol, was associated with the incidence of CHD independent of traditional risk factors (TRFs) (HR = 1.50; 95%CI = 1.12-2.01). Predictive performance of this metabolite score on its own was moderate (C-index = 0.75; 95%CI = 0.70-0.80) but after adding age and sex the C-index was only modestly lower than that of TRFs (C-index = 0.81; 95%CI = 0.77-0.85 and C-index = 0.82; 95%CI = 0.78-0.87, respectively). The metabolite score was also associated with prevalent CHD independent of TRFs (OR = 1.59; 95%CI = 1.19-2.13).
A metabolite score derived from a single-point metabolome measurement is associated with CHD and metabolomics may be a promising tool for refining and improving the prediction of CHD.
[Show abstract][Hide abstract] ABSTRACT: To study the association between occupational asbestos exposure and pleural mesothelioma, lung cancer, and laryngeal cancer, specifically addressing risk associated with the lower end of the exposure distribution, risk of cancer subtypes, and the interaction between asbestos and smoking.
Using the Netherlands Cohort Study (n = 58,279 men, aged 55 to 69 years), asbestos exposure was estimated by linkage to job-exposure matrices. After 17.3 years of follow-up, 132 pleural mesothelioma, 2324 lung cancer, and 166 laryngeal cancer cases were available.
The multivariable-adjusted model showed overall positive associations between all levels of asbestos exposure and mesothelioma, lung cancer, and laryngeal cancer. Lung adenocarcinoma and glottis cancer showed only a positive association after prolonged higher asbestos exposure (hazard ratio per 10 years increment, 1.43 [95% confidence interval, 1.06 to 1.93] and 1.95 [95% confidence interval, 1.36 to 2.80], respectively). There was no statistically significant interaction between asbestos and smoking.
Asbestos levels encountered at the lower end of the exposure distribution may be associated with an increased risk of pleural mesothelioma, lung cancer, and laryngeal cancer.
Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 12/2013; · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC.Methods:The Netherlands Cohort Study (NLCS) with case-cohort design included 120 852 participants aged 55-69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses.Results:Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02).Conclusion:Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.British Journal of Cancer advance online publication, 10 December 2013; doi:10.1038/bjc.2013.771 www.bjcancer.com.
British Journal of Cancer 12/2013; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are few epidemiological data on the dietary risk factors of Barrett's oesophagus, a precursor of oesophageal adenocarcinoma. The present study investigated the association between vegetable, fruit and nitrate intake and Barrett's oesophagus risk in a large prospective cohort. The Netherlands Cohort Study recruited 120 852 individuals aged 55-69 years in 1986. Vegetable and fruit intake was assessed using a 150-item FFQ, and nitrate intake from dietary sources and drinking water was determined. After 16·3 years of follow-up, 433 cases (241 men and 192 women) of Barrett's oesophagus with specialised intestinal metaplasia and 3717 subcohort members were analysed in a case-cohort design using Cox proportional hazards models while adjusting for potential confounders. Men exhibited a lower risk of Barrett's oesophagus in the highest v. the lowest quintile of total (multivariable-adjusted hazard ratio (HR): 0·66, 95 % CI 0·43, 1·01), raw (HR 0·63, 95 % CI 0·40, 0·99), raw leafy (HR 0·55, 95 % CI 0·36, 0·86) and Brassica (HR 0·64, 95 % CI 0·41, 1·00) vegetable intake. No association was found for other vegetable groups and fruits. No significant associations were found between vegetable and fruit intake and Barrett's oesophagus risk among women. Total nitrate intake was inversely associated with Barrett's disease risk in men (HR 0·50, 95 % CI 0·25, 0·99) and positively associated with it in women (HR 3·77, 95 % CI 1·68, 8·45) (P for interaction = 0·04). These results suggest that vegetable intake may contribute to the prevention of Barrett's oesophagus. The possible differential effect in men and women should be evaluated further.
The British journal of nutrition 12/2013; · 3.45 Impact Factor