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Supplementary Table 1. Multivariable-adjusted hazard rate ratios (HRs) and 95% CI for lymphoid and myeloid neoplasms according to quintiles of mono- and polyglutamate intake (men and women); Netherlands Cohort Study on diet and cancer, 1986-2003.

Supplementary Table 2 from A Prospective Cohort Study on Overweight, Smoking, Alcohol Consumption, and Risk of Barrett's Esophagus

Supplementary Table 3 from A Prospective Cohort Study on Overweight, Smoking, Alcohol Consumption, and Risk of Barrett's Esophagus

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 and 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 vs. lowest quintile: HR = 1.87; 95% confidence intervals, 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 nonsignificant 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 nonsignificant 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. Cancer Epidemiol Biomarkers Prev; 23(10); 2153–64. ©2014 AACR.

Background: Barrett's esophagus (BE) is a precursor lesion of esophageal adenocarcinoma. Besides gastroesophageal reflux, possible risk factors for BE include overweight, cigarette smoking, and alcohol consumption. Our objective was to study these associations by using prospective data.Methods: The prospective Netherlands Cohort Study, initiated in 1986, consists of 120,852 men and women, aged 55 to 69 years at baseline. At baseline, all subjects completed a questionnaire on dietary habits and lifestyle. After 16.3 years of follow-up, 370 BE cases with specialized intestinal metaplasia and 3,866 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR) and 95% CIs.Results: Body mass index (BMI) at baseline was associated with risk of BE in women [multivariable adjusted RR per 1 kg/m2, 1.07 (1.03–1.11)] but not in men [RR per 1 kg/m2, 0.99 (0.93–1.05)]. The association in women was not specifically due to abdominal overweight. Former cigarette smokers were at increased risk of BE (RR = 1.33, 95% CI: 1.00–1.77), but current smokers were not. Smoking duration showed a positive association with BE risk (Ptrend = 0.03). For alcohol consumption, the RR per 10 g ethanol/d was 0.95 (0.87–1.03).Conclusions: Increased BMI was a risk factor for BE in women but not in men. Several aspects of cigarette smoking were positively associated with BE risk. Alcohol consumption was not associated with an increased risk of BE.Impact: Future research should focus on risk factors both for development and for progression of BE to esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 20(2); 345–58. ©2010 AACR.

Supplementary Table 1 from A Prospective Cohort Study on Overweight, Smoking, Alcohol Consumption, and Risk of Barrett's Esophagus

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥ 45 vs.

Study Design Prospective cohort design using data derived from usual care. Background It is important that patients are able to function independently as soon as possible after total hip replacement. However, the speed of regaining activities differs significantly. Objectives To develop a risk stratification model (RSM) to predict delayed inpatient recovery of physical activities in people who underwent total hip replacement surgery. Methods This study was performed in 2 routine orthopaedic settings: Diakonessenhuis Hospital (setting A) and Nij Smellinghe Hospital (setting B). Preoperative screening was performed for all consecutive patients. In-hospital recovery of activities was assessed with the Modified Iowa Level of Assistance Scale. Delayed inpatient recovery of activities was defined as greater than 5 days. The RSM, developed using logistic regression analysis and bootstrapping, was based on data from setting A (n = 154). External validation was performed on the data set from setting B (n = 271). Results Twenty-one percent of the patients in setting A had a delayed recovery of activities during their hospital stay. Multivariable logistic regression modeling yielded a preliminary RSM that included the following factors: male sex (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.2, 2.6), 70 or more years of age (OR = 1.2; 95% CI: 0.4, 3.4), body mass index of 25 kg/m2 or greater (OR = 2.2; 95% CI: 0.7, 7.4), an American Society of Anesthesiologists score of 3 (OR = 1.2; 95% CI: 0.3, 4.4), a Charnley score of B or C (OR = 6.1; 95% CI: 2.2, 17.4), and a timed up-and-go score of 12.5 seconds or greater (OR = 3.1; 95% CI: 1.1, 9.0). The area under the receiver operating characteristic (ROC) curve was 0.82 (95% CI: 0.74, 0.90) and the Hosmer-Lemeshow test score was 3.57 (P>.05). External validation yielded an area under the ROC curve of 0.71 (95% CI: 0.61, 0.81). Conclusion We demonstrated that the risk for delayed recovery of activities during the hospital stay can be predicted by using preoperative data.

There is limited prospective data on the relationship between consumption of vegetables and fruits and the risk of head-neck cancer (HNC) subtypes [i.e., oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC) and laryngeal cancer (LC)]. Therefore, we investigated these associations within the Netherlands Cohort Study, in which 120,852 participants completed a 150-item food frequency questionnaire at baseline in 1986. After 20.3 years of follow-up, 415 cases of HNC (131 OCC, 88 OHPC, three oral cavity/pharynx unspecified or overlapping and 193 LC) and 3,898 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Total vegetable and fruit consumption was inversely associated with risk of HNC overall [multivariable-adjusted rate ratios for highest vs. lowest quartile: 0.61, 95% confidence interval (CI) 0.44-0.85, p trend 0.002] and all HNC subtypes, with the strongest associations for OCC. Total vegetable intake and total fruit intake were also associated with a decreased risk of HNC overall and HNC subtypes. No significant interaction was found between vegetable and fruit intake and alcohol consumption or cigarette smoking. In conclusion, in this large-scale cohort study, consumption of vegetables and fruits was associated with a decreased risk of HNC overall and all subtypes. Consumption of vegetables and fruits (or of specific groups of them) may protect against HNC and its subtypes.

The evidence for an association between occupational asbestos exposure and esophageal, gastric and colorectal cancer is limited. We studied this association specifically addressing risk differences between relatively low and high exposure, risk associated with cancer subtypes, the influence of potential confounders and the interaction between asbestos and smoking in relation to cancer risk. Using the Netherlands Cohort Study (n = 58,279 men, aged 55-69 years at baseline), asbestos exposure was estimated by linkage to a job-exposure matrix. After 17.3 years of follow-up, 187 esophageal, 486 gastric and 1,724 colorectal cancer cases were available for analysis. The models adjusted for age and family history of cancer showed that mainly (prolonged) exposure to high levels of asbestos was statistically significantly associated with risk of esophageal adenocarcinoma (EAC), total and distal colon cancer and rectal cancer. For overall gastric cancer and gastric non-cardia adenocarcinoma (GNCA), also exposure to lower levels of asbestos was associated. Additional adjustment for lifestyle confounders, especially smoking status, yielded non-significant associations with overall gastric cancer and GNCA in the multivariable-adjusted model, except for the prolonged highly exposed subjects (tertile 3 vs. never: HR 2.67, 95% CI: 1.11-6.44 and HR 3.35, 95% CI: 1.33-8.44, respectively). No statistically significant additive or multiplicative interaction between asbestos and smoking was observed for any of the studied cancers. This prospective population-based study showed that (prolonged) high asbestos exposure was associated with overall gastric cancer, EAC, GNCA, total and distal colon cancer and rectal cancer. © 2014 UICC.

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 (CRC) 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 CRC risk characterized by mutations in Kirsten-ras (KRAS) and adenomatous polyposis coli (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 (HR) 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 fourth versus first quartile: 2.12 [95% confidence interval (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 (fourth versus first quartile: 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 CRC with specific somatic mutations, differentially in men and women. More research is needed to corroborate or refute these findings.

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. © © The Author 2013.

Results from epidemiological studies suggest that alcohol drinkers have a decreased risk of lymphoid neoplasms, whereas results for myeloid neoplasms are inconsistent. However, most of these studies have used retrospective data. We examined prospectively whether alcohol consumption decreases the risk of both lymphoid and myeloid neoplasms, including most common subtypes. Moreover, we investigated whether this decreased risk is due to ethanol or other contents of specific alcoholic beverages (i.e., beer, wine and liquor). The Netherlands cohort study consisted of 120,852 individuals who completed a baseline questionnaire in 1986. After 17.3 years of follow-up, 1,375 cases of lymphoid and 245 cases of myeloid neoplasms with complete exposure information were available for analysis. Compared with abstinence, we observed for plasma cell neoplasms hazard rate ratios (HR) of 1.66 (95% confidence interval (CI), 1.21-2.29), 1.63 (95% CI, 1.17-2.27), 1.11 (95% CI, 0.75-1.64) and 0.85 (95% CI, 0.51-1.42) with daily ethanol consumption of 0.1

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.

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC); however, studies differentiating between subsites of CRC are limited. We investigated how diabetes mellitus (DM) was associated with subsite-specific CRC risk in men and women. Methods The Netherlands Cohort Study on diet and cancer is a prospective study among 120 852 men and women aged 55-69 years old at baseline in 1986. Information on DM, anthropometric, dietary and lifestyle factors was self-reported at baseline. T2DM was defined as the diagnosis of DM after 30 years of age. Incident CRC cases were identified by record linkage with the Netherlands cancer registry and the Dutch pathology registry. After 17.3 years of follow-up, 1735 incident male CRC cases and 1321 female CRC cases were available for analyses. Subsite-specific hazard ratios (HRs) for CRC were estimated in case-cohort analyses using Cox regression. Results At baseline, 3.1% of subcohort members reported T2DM, of whom 80% were diagnosed after 50 years of age. Multivariable-adjusted models showed that the risk of proximal colon cancer was significantly increased in women with T2DM versus women without T2DM (HR = 1.80, 95% confidence interval: 1.10-2.94). There was no association between T2DM and the risk of overall CRC, distal colon cancer and rectal cancer in women. In men, T2DM was not associated with overall CRC (HR=0.98, 95% confidence interval: 0.64-1.50), or with risk at any subsite. Conclusions This prospective study showed an increased risk of proximal colon cancer in women with T2DM compared with non-T2DM women. Eur J Gastroenterol Hepatol 28:896-903

Background How body size influences risk of molecular subtypes of colorectal cancer (CRC) is unclear. We investigated whether measures of anthropometry differentially influence risk of tumours according to BRAF c.1799T>A p.V600E mutation (BRAF) and microsatellite instability (MSI) status. Methods Data from The Netherlands Cohort Study (n = 120 852) and Melbourne Collaborative Cohort Study (n = 40 514) were pooled and included 734 and 717 colorectal cancer cases from each study, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), waist measurement and height were calculated and compared for subtypes defined by BRAF mutation and MSI status, measured from archival tissue. Results Results were consistent between studies. When pooled, BMI modelled in 5 kg/m increments was positively associated with BRAF wild-type (HR: 1.16, 95% CI: 1.08-1.26) and MS-stable tumours (HR: 1.15, 95% CI: 1.06-1.24). Waist measurement was also associated with BRAF wild-type (highest vs lowest quartile, HR: 1.59, 95% CI: 1.33-1.90) and MS-stable tumours (highest vs lowest quartile HR: 1.68, 95% CI: 1.31-2.15). The HRs for BRAF mutation tumours and MSI tumours were smaller and non-significant, but differences between the HRs by tumour subtypes were not significant. Height, modelled per 5-cm increase, was positively associated with BRAF wild-type and BRAF mutation tumours, but the HR was greater for tumours with a BRAF mutation than BRAF wild-type (HR: 1.23, 95% CI: 1.11-1.37, P = 0.03). Similar associations were observed with respect to height and MSI tumours (HR: 1.26, 95% CI: 1.13-1.40, P = 0.02). Conclusions Generally, overweight increases the risk of CRC. Taller individuals have an increased risk of developing a tumour with a BRAF mutation or MSI. Published by Oxford University Press on behalf of the International Epidemiological Association

Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: -0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.

Food consumption causes, together with mobility, shelter and the use of electrical products, most life cycle impacts of consumption. Meat and dairy are among the highest contributors to environmental impacts from food consumption. A healthier diet might have less environmental impacts. Using the E3IOT environmentally extended input output database developed in an EU study on Environmental Impacts of Products (EIPRO), this paper estimates the difference in impacts between the European status quo and three simulated diet baskets, i.e. a pattern according to universal dietary recommendations, the same pattern with reduced meat consumption, and a 'Mediterranean' pattern with reduced meat consumption. Production technologies, protein and energy intake were kept constant. Though this implies just moderate dietary shifts, impact reductions of up to 8% were possible in reduced meat scenarios. The slightly changed food costs do not lead to significant first order rebound effects. Second order rebounds were estimated by applying the CAPRI partial equilibrium model. This analysis showed that European meat production sector will most likely respond by higher exports to compensate for losses on the domestic meat market. Higher impact reductions probably would need more drastic diet changes. © 2011 Elsevier B.V.

Background: The consumption of dairy products (milk, cheese, and butter) has been positively associated with the risk of ischemic heart disease (IHD), stroke, and total mortality because of the saturated fat content of these products; and protective effects against these outcomes have been attributed to the calcium content and low-fat choices of dairy products. However, robust evidence on the net effect of dairy product consumption on mortality is limited. Objective: The objective was to investigate the association between dairy product consumption and the risk of death (from all causes, IHD, and stroke) in the Netherlands Cohort Study (NLCS). Design: The NLCS was initiated in 120,852 men and women aged 55-69 y at baseline in 1986. After 10 y of follow-up, 16,136 subjects with complete dietary information had died. Twenty-nine percent (men) and 22% (women) of these deaths were due to IHD or stroke. The validated 150-item food-frequency questionnaire provided detailed information on dairy products. Results: Multivariate survival analyses following a case-cohort approach showed only a few statistically significant, but mostly weak, associations. A slightly increased risk of all-cause and IHD mortality was found for both butter and dairy fat intake (per 10 g/d; rate ratiomortality: 1.04; 95% CI: 1.01, 1.06) only in women. Fermented full-fat milk was inversely associated with all-cause and nonsignificantly with stroke mortality in both sexes. Conclusions: The role of dairy product consumption in mortality generally appeared to be neutral in men. In women, dairy fat intake was associated with slightly increased all-cause and IHD mortality. More research is warranted on a possible protective effect of fermented milk on stroke mortality. © 2011 American Society for Nutrition.

Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). Among 609 CRC cases and 1,663 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852), we estimated CRC risk according to methyl donor intake across genotypes of folate metabolizing enzymes and methyltransferases. Although diet-gene interactions were not statistically significant, methionine intake was inversely associated with CRC among subjects having both common rs2424913 and rs406193 DNMT3B C > T genotypes (highest versus lowest tertile: RR = 0.44; p trend = 0.05). Likewise, vitamin B2 was modestly inversely associated among individuals with the MTHFR c.665CC (rs1801133) genotype (RR = 0.66; p trend = 0.08), but with a significant reduced risk when ≤ 1 rare allele occurred in the combination of folate metabolizing enzymes MTHFR, MTRR and MTR (RR = 0.30; p trend = 0.005). Folate or vitamin B6 were neither inversely associated with CRC nor was methyl donor intake associated with the CpG island methylator phenotype (CIMP). Despite the absence of heterogeneity across genotypes, might an effect of methyl donors on CRC be more pronounced among individuals carrying common variants of folate metabolizing enzymes or DNA methyltransferases. Combining genotypes may assist to reveal diet associations with CRC, possibly because rare variants of related genes may collectively affect specific metabolic pathways or enzymatic functions. © 2010 The Author(s). methyltransferase, 9037-42-7; cytosine, 71-30-7; methionine, 59-51-8, 63-68-3, 7005-18-7; methyltransferase, 9033-25-4; pyridoxine, 12001-77-3, 58-56-0, 65-23-6, 8059-24-3; riboflavin, 83-88-5; thymine, 65-71-4

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. © 2011 American Society for Nutrition.

The authors investigated the associations between bowel movement and constipation frequencies and colorectal cancer (CRC) endpoints among men in the Netherlands Cohort Study on Diet and Cancer (n = 58,279) and explored whether dietary fiber intake may modify associations. After 13.3 years (1986-1999), 1,207 CRC cases and 1,753 subcohort members were available for case-cohort analyses. Multivariate analyses showed a significantly increased hazard ratio for CRC overall and rectal cancer in men who reported having a bowel movement 1-2 times per day (second-highest category) as compared with once a day (CRC: hazard ratio (HR) = 1.29, 95% confidence interval (CI): 1.09, 1.53 (P(trend)

Chronic mild dehydration has been associated with several diseases, including fatal IHD and stroke. It has been suggested that hydration through total fluid intake (or water) is inversely associated with IHD or stroke mortality. The objective of the present study was to evaluate the relationship between total fluid (and specific beverage) intake and IHD or stroke mortality in the Netherlands Cohort Study (NLCS). In 1986, 120 852 participants aged 55–69 years were enrolled into the NLCS. Mortality data were collected over a 10-year follow-up period. Analysis was done through a case–cohort approach, and it was based on the subjects without a history of heart disease, stroke or diabetes at baseline. A total of 1789 IHD mortality cases and 708 stroke mortality cases occurred during the follow-up. Higher total fluid consumption was not associated with either IHD mortality or stroke mortality in men or women. When analysing specific beverages, a positive association between coffee consumption (increment 270 ml/d) and IHD mortality was observed in men (hazard ratio (HR) 1·09, 95 % CI 1·00, 1·18), while an inverse relationship was observed in women (HR: 0·88, 95 % CI 0·78, 1·00). For tea consumption (increment of 253 ml/d), an inverse relationship with IHD mortality was observed in men (HR: 0·91, 95 % CI 0·83, 1·00). No association with water intake was observed. In the study population, fresh water consumption was very low. In conclusion, total fluid intake was not associated with IHD or stroke mortality in either men or women. Coffee consumption was inversely associated with IHD mortality in women only, while a higher tea intake was associated with lower IHD mortality in men only.

Acrylamide, a potential human carcinogen, has been discovered in a variety of heat-treated carbohydrate-rich food products. Previously, dietary acrylamide intake was shown to be associated with endocrine-related cancers in humans. We assessed the association between dietary acrylamide intake and risk of postmenopausal breast cancer stratified by estrogen and progesterone receptor status. This study was embedded within the Netherlands Cohort Study on diet and cancer, which was initiated in 1986 enrolling 62,573 women aged 55-69 years at baseline. After 13.3 years of follow-up, 2225 incident breast cancer cases were ascertained, with hormone receptor status information for 43%. Cox proportional hazards analysis was applied to determine hazard ratios in quintiles of dietary acrylamide intake stratifying on estrogen receptor (ER) and progesterone receptor (PR) and smoking status. No association was observed for overall breast cancer or receptor-negative breast cancer risk, irrespective of smoking status. A statistically non-significantly increased risk of ER positive, PR positive and joint receptor-positive breast cancer was found in never-smoking women. The multivariable-adjusted hazard ratios were 1.31 (95% CI: 0.87-1.97, P trend = 0.26) for ER+, 1.47 (0.86-2.51, P trend = 0.14) for PR+, and 1.43 (0.83-2.46, P trend = 0.16) for ER+PR+, when comparing women in the highest quintile of acrylamide intake (median 36.8 μg/day) to women in the lowest (median 9.5 μg/day). This study showed some indications of a positive association between dietary acrylamide intake and receptor-positive breast cancer risk in postmenopausal never-smoking women. Further studies are needed to confirm or refute our observations. © 2009 Springer Science+Business Media, LLC.

Background: 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. Methods: 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. Results: 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 ≥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. Conclusions: 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. Impact: Quitting smoking would benefit the burden on pancreatic cancer incidence. Cancer Epidemiol Biomarkers Prev; 19(6); 1612–22. ©2010 AACR.

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 (RRper 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 (0.72; 95% CI: 0.61-0.84 RRper standard umt Increment) and RRper 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.

Contains fulltext : 88671.pdf (Publisher’s version ) (Closed access) PURPOSE: Body mass index (BMI) is an important risk factor for clear-cell renal cancer (cc-RCC). A common molecular alteration in cc-RCC is loss-of-function of the von Hippel-Lindau (VHL) gene. We evaluated the association between BMI and VHL mutations in cc-RCC by using data from the Netherlands Cohort Study (NLCS), a prospective study, which comprises 120,852 persons. METHODS: After 11.3 years of follow-up, 337 incident RCC cases were identified; 185 cc-RCC cases were included for analyses. RESULTS: A high BMI at baseline was associated with an increased risk of cc-RCC with or without VHL mutations (per 1 kg/m(2): hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 1.02-1.16 and HR = 1.08, 95%CI: 1.01-1.15, respectively). BMI at age 20 was only associated with an increased risk of cc-RCC with VHL mutations (per 1 kg/m(2): HR =1.09, 95% CI: 1.03-1.16). In contrast, BMI gain since age 20 was only associated with an increased risk in VHL wild-type cases (per 1 kg/m(2): HR = 1.10, 95% CI: 1.03-1.19). CONCLUSION: Our findings indicate that BMI may be differently associated with subtypes of RCC based on VHL mutations. 01 mei 2010

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. =1,000 ml/day: HR = 1.50, 95% CI = 0.95-2.37, P trend = 0.08) and a significant positive trend for coffee intake (>6 vs. =2 cups/day: HR = 1.60, 95% CI = 0.96-2.66, P trend = 0.05). However, a nonsignificant positive trend for total fluid intake was no longer observed when additionally adjusting for coffee intake. Tests for interaction were not significant. In conclusion, total fluid intake was not associated with colorectal cancer risk in either men or women. There was no evidence that fiber intake modified associations. Of the specific beverages, coffee intake was positively associated with rectal cancer risk in men. Copyright © 2010, Taylor & Francis Group, LLC.

BACKGROUND: Conflicting results on the relationship between the hardness of drinking water and mortality related to ischemic heart disease (IHD) or stroke have been reported. OBJECTIVES: We investigated the possible association between tap water calcium or magnesium concentration and total hardness and IHD mortality or stroke mortality. METHODS: In 1986, a cohort of 120,852 men and women aged 55-69 years provided detailed information on dietary and other lifestyle habits. Follow-up for mortality until 1996 was established by linking data from the Central Bureau of Genealogy and Statistics Netherlands. We calculated tap water hardness for each postal code using information obtained from all pumping stations in the Netherlands. Tap water hardness was categorized as soft [ 2.0 mmol/L CaCO(3)). The multivariate case-cohort analysis was based on 1,944 IHD mortality and 779 stroke mortality cases and 4,114 subcohort members. RESULTS: For both men and women, we observed no relationship between tap water hardness and IHD mortality [hard vs. soft water: hazard ratio (HR) = 1.03; 95% confidence interval (CI), 0.85-1.28 for men and HR = 0.93; 95% CI, 0.71-1.21 for women) and stroke mortality (hard vs. soft water HR = 0.90; 95% CI, 0.66-1.21 and HR = 0.86; 95% CI, 0.62-1.20, respectively). For men with the 20% lowest dietary magnesium intake, an inverse association was observed between tap water magnesium intake and stroke mortality (HR per 1 mg/L intake = 0.75; 95% CI, 0.61-0.91), whereas for women with the 20% lowest dietary magnesium intake, the opposite was observed. CONCLUSIONS: We found no evidence for an overall significant association between tap water-hardness, magnesium or calcium concentrations, and IHD mortality or stroke mortality. More research is needed to investigate the effect of tap water magnesium on IHD mortality or stroke mortality in subjects with low dietary magnesium intake.

Since 2002, it is known that the probable human carcinogen acrylamide is present in commonly consumed carbohydrate-rich foods, such as French fries and potato chips. In this review, the authors discuss the body of evidence on acrylamide carcinogenicity from both epidemiological and rodent studies, including variability, strengths and weaknesses, how both types of evidence relate, and possible reasons for discrepancies. In both rats and humans, increased incidences of various cancer types were observed. In rats, increased incidences of mammary gland, thyroid tumors and scrotal mesothelioma were observed in both studies that were performed. In humans, increased risks of ovarian and endometrial cancers, renal cell cancer, estrogen (and progesterone) receptor-positive breast cancer, and oral cavity cancer (the latter in non-smoking women) were observed. Some cancer types were found in both rats and humans, e.g., endometrial cancer (observed in one of the two rat studies), but there are also some inconsistencies. Interestingly, in humans, some indications for inverse associations were observed for lung and bladder cancers in women, and prostate and oro- and hypopharynx cancers in men. These latter observations indicate that genotoxicity may not be the only mechanism by which acrylamide causes cancer. The estimated risks based on the epidemiological studies for the sites for which a positive association was observed were considerably higher than those based on extrapolations from the rat studies. The observed pattern of increased risks in the rat and epidemiological studies and the decreased risks in the epidemiological studies suggests that acrylamide might influence hormonal systems, for which rodents may not be good models.

The authors examined the association between the intake of different dairy products and the risk of bladder cancer in 120,852 men and women aged 55-69 years participating in the Netherlands Cohort Study on Diet and Cancer. Dairy product intake was assessed in 1986 by using a 150-item food frequency questionnaire. The cohort was followed for 16.3 years, and 1,549 incident cases of bladder cancer were analyzed. Cox proportional hazards analysis was applied with a case-cohort approach by using the follow-up data of a random subcohort (n = 5,000). Multivariate hazard ratio estimates comparing the highest with the lowest quintile of total dairy intake were 1.01 (95% confidence interval (CI): 0.81, 1.27; P(trend) = 0.68). A statistically significant association for fermented milk products was found only for the second quintile (median, 12 g/day) (hazard ratio = 0.71, 95% CI: 0.56, 0.91). Compared with nonconsumers, women with 25-75 g/day of butter consumption had a hazard ratio of 1.61 (95% CI: 1.03, 2.50; P(trend)

The authors automated the selection of foods in a computer system that compiles and processes tailored FFQ. For the selection of food items, several methods are available. The aim of the present study was to compare food lists made by MOM2, which identifies food items with highest between-person variance in intake of the nutrients of interest without taking other items into account, with food lists made by forward regression. The name MOM2 refers to the variance, which is the second moment of the nutrient intake distribution. Food items were selected for the nutrients of interest from 2 d of recorded intake in 3524 adults aged 25–65 years. Food lists by 80 % MOM2 were compared to those by 80 % explained variance for regression on differences between the number and type of food items, and were evaluated on (1) the percentage of explained variance and (2) percentage contribution to population intake computed for the selected items on the food list. MOM2 selected the same food items for Ca, a few more for fat and vitamin C, and a few less for carbohydrates and dietary fibre than forward regression. Food lists by MOM2 based on 80 % of variance in intake covered 75–87 % of explained variance for different nutrients by regression and contributed 53–75 % to total population intake. Concluding, for developing food lists of FFQ, it appears sufficient to select food items based on the contribution to variance in nutrient intake without taking covariance into account.

Dietary flavonoids are hypothesized to be protective against colorectal cancer, yet findings have been inconsistent. We examined the association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints within the Netherlands Cohort Study (NLCS). In addition, we explored whether body mass index (BMI) may be an effect modifier of this association. The NLCS includes 120,852 men and women who were 55-69 years and completed a self-administered questionnaire at baseline in 1986. A case-cohort approach was used for data processing and analysis. After 13.3 years, 1,444 male and 1,041 female colorectal cancer cases were available for estimation of hazard ratios and 95% confidence intervals for quintiles of flavonoid intake. After adjustment for potential confounders, no association of total flavonol and flavone intake and total catechin intake with colorectal cancer endpoints was observed. Analyses stratified for BMI showed significant inverse trends in the association of total catechin intake, (+)-catechin intake and (-)-epicatechin intake with rectal cancer in men with a BMI ≥ 25 kg/m2 and in the association of total catechin intake and intake of kaempferol, myricetin and all individual catechins with colorectal cancer, in particular colon cancer, in women with a BMI < 25 kg/m2. In conclusion, our findings generally do not support an association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints. Dietary catechin intake may be associated with a decreased rectal cancer risk in overweight men. Dietary flavonol and catechin intake may be associated with a decreased colorectal cancer risk in normal weight women. © 2009 UICC.

BACKGROUND: Few studies have considered the potential utility of clothing size as a predictor of diseases associated with body weight. METHODS: We used data on weight-stable men and women from a subcohort of the Netherlands Cohort Study to assess the correlation of clothing size with other anthropometric variables. Cox regression using the case-cohort approach was performed to establish whether clothing size can predict cancer risk after 13.3 years of follow-up, and if additionally considering body mass index (BMI) in the model improves the prediction. RESULTS: Trouser and skirt size correlated well with circumference measurements. Skirt size predicted endometrial cancer risk, and this effect was slightly attenuated when BMI was added to the model. Trouser size predicted risk of renal cell carcinoma, regardless of whether BMI was in the model. CONCLUSIONS: Clothing size appears to predict cancer risk independently of BMI, suggesting that clothing size is a useful measure to consider in epidemiologic studies when waist circumference is not available. © 2009 Lippincott Williams & Wilkins, Inc.

Background: Acrylamide is a probable human carcinogen, which is present in several heat-treated foods. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamide administration in drinking water to rats. In the current study, the association between dietary acrylamide intake and human brain cancer risk was investigated for the first time. Methods: In 1986, 120,852 persons (ages 55-69 years) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5,000 participants was randomly selected from the total cohort for a case-cohort approach. Acrylamide intake was assessed with a food frequency questionnaire at baseline and based on acrylamide analyses in relevant Dutch foods. Hazard ratios (HR) were calculated using Cox proportional hazards analysis. Subgroup analyses were done for microscopically verified brain cancer, astrocytic gliomas, high-grade astrocytic gliomas, and never-smokers. The acrylamide risk estimates were adjusted for possible brain cancer risk factors. Results: After 16.3 years of follow-up, 216 brain cancer cases were available for analysis. The multivariable-adjusted HR per 10 μg/d increment of acrylamide intake was 1.02 (95% confidence interval, 0.89-1.16). HRs were not significantly increased either when dietary acrylamide intake was analyzed as a categorical variable. Also, there was no association in the subgroups based on histology and smoking. Conclusion: In this prospective cohort study, acrylamide intake was not associated with brain cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1663–6)

Background : Acrylamide is a probable human carcinogen that is present in several heat-treated foods. In epidemiological studies, positive associations between dietary acrylamide intake and the risks of endometrial, ovarian, estrogen receptor-positive breast, and renal cell cancers have been observed. The association between dietary acrylamide intake and lung cancer risk is not known. Methods : We conducted a case-cohort study among 58-279 men and 62-573 women (aged 55-69 years) in the Netherlands Cohort Study on Diet and Cancer. Intakes of acrylamide-containing foods and risk factors for cancer were assessed with a self-administered questionnaire at baseline in 1986 and combined with acrylamide levels in relevant Dutch foods to assess total dietary acrylamide intake. The number of person-years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n = 5000). Incident lung cancer cases in the total cohort were detected by computerized record linkages to the Netherlands Cancer Registry and the Netherlands Pathology Registry. Hazard ratios and 95% confidence intervals (CIs) for the risk of lung cancer associated with acrylamide intakes were estimated using Cox proportional hazards models that controlled for smoking (status, quantity, and duration) and other lung cancer risk factors. All statistical tests were two-sided. Results : After 13.3 years of follow-up (September 17, 1986 up to January 1, 2000) there were 2649 cases of primary, histologically verified lung cancer (International Classification of Diseases for Oncology-3 code: C34) when cases with prevalent cancer at baseline (other than skin cancer) were excluded. The multivariable-adjusted hazard ratio of lung cancer for a 10-μg/d increment of acrylamide intake was 1.03 (95% CI = 0.96 to 1.11) for men and 0.82 (95% CI = 0.69 to 0.96) for women. The hazard ratio of lung cancer for the highest (median intake [μg/d]: men = 37.6 and women = 36.8) vs the lowest (median intake [μg/d]: men = 10.8 and women = 9.5) quintile of acrylamide intake was 1.03 (95% CI = 0.77 to 1.39, Ptrend =.85) for men and 0.45 (95% CI = 0.27 to 0.76, Ptrend =.01) for women. The inverse association in women was strongest for adenocarcinoma (hazard ratio for highest vs lowest tertile of intake = 0.40, 95% CI = 0.21 to 0.78; Ptrend =.01). Conclusions : Acrylamide intake was not associated with lung cancer risk in men but was inversely associated in women, most strongly for adenocarcinoma. This finding suggests that acrylamide is involved in human carcinogenesis through pathways other than genotoxicity. © 2009 Oxford University Press.

Meat contains numerous carcinogens, such as heterocyclic amines, polycyclic aromatic hydrocarbons, and N-nitroso compounds, which can be derived either from natural food or during the process of food preparation. These carcinogens may increase pancreatic cancer risk. Furthermore, studies in animals showed that polyunsaturated fatty acids, especially linoleic acid, increase pancreatic cancer risk. We examined prospectively the relation between pancreatic cancer risk and intake of fresh meat, processed meat, fish, eggs, total fat, and different types of fat. The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 13.3 years of follow-up, 350 pancreatic cancer cases (66% microscopically confirmed) were available for analysis. A validated 150-item food-frequency questionnaire was used to calculate intake of fresh meat, processed meat, fish, eggs, fat and different types of fat. No association was found when examining the association between intake of fresh meat, other types of meat, fish, eggs, dietary intake of total fat and different types of fat and risk of pancreatic cancer. It is important for future studies to investigate the relation between different meat-cooking methods and pancreatic cancer. © 2009 UICC.

This study examined the relationship between diet-related parenting practices, parental characteristics, child characteristics, and 2-year-old child's dietary intake. Cross-sectional data (N = 2578) originated from the KOALA Birth Cohort Study. Principal component analyses revealed two restrictive parenting practice clusters: a cluster characterized by prohibition of the intake of various snacks and soft drinks, and a separate cluster characterized by prohibition of cookies and cake. Regression analyses showed that these clusters were related to the children's behavioural style (i.e. oppositional, depressive and/or aggressive behaviour) and to educational level, age and alternative lifestyle of the mother. The clusters also had a favourable influence on dietary intake (i.e. restrictive parenting practices were related to less consumption of the restricted (unhealthy) items and higher consumption of items considered to be healthy), which was moderated by child characteristics. The parenting practices showed a stronger association with dietary intake in children with a favourable behavioural style (i.e. non-depressed, low anxious, low overactive), a favourable eating style or a lower BMI. The findings suggest opportunities for preventive interventions focussing on parents of young children, and indicate that different approaches to parenting practice interventions are needed for different types of children. © 2008 Elsevier Ltd. All rights reserved.

Acrylamide is a probable human carcinogen that was detected in several heat-treated foods, such as French fries and crisps, in 2002. Prospective studies are needed on acrylamide and human cancer risk. We prospectively investigated the association between acrylamide and gastrointestinal cancer risk. In 1986, 120,852 men and women (aged 55-69 y) were included in the Netherlands Cohort Study on diet and cancer. At baseline, a random subcohort of 5000 participants was selected for a case-cohort approach. Acrylamide intake was assessed with a FFQ at baseline and was based on acrylamide analyses in relevant Dutch foods. After 13.3 y of follow-up, 2190, 563, 349, and 216 cases of colorectal, gastric, pancreatic, and esophageal cancer, respectively, were available for analysis. The daily acrylamide intake of the subcohort was (mean ± SD) 21.7 ± 12.1μg. A 10-μg/d increment of acrylamide intake was associated with multivariable-adjusted Cox proportional hazard rate ratios (HR) (95% CI) of 1.00 (0.96-1.06), 1.02 (0.94-1.10), 1.06 (0.96-1.17), and 0.96 (0.85-1.09) for colorectal, gastric, pancreatic, and esophageal cancer, respectively. For former or never-smokers, the corresponding HR were: 1.03 (0.94-1.12), 1.09 (0.98-1.22), 1.07 (0.93-1.24), and 0.92 (0.76-1.11). There were some significantly increased risks within subgroups stratified by obesity, nonoccupational physical activity, and age, factors that were a priori selected based on their capacity to modify cytochrome P4502E1 activity. Overall, acrylamide intake was not associated with colorectal, gastric, pancreatic, and esophageal cancer risk, but some subgroups deserve further attention. © 2008 American Society for Nutrition.

Familial clustering of cancer is expected to occur at practically all anatomical sites. However, few studies have had sufficient size to investigate different sites simultaneously and with adjustment for confounders. We evaluated familial clustering in the Netherlands Cohort Study in which 120,852 men and women, aged 55-69 years in 1986 were followed up for 13.3 years. 14,025 Probands, 6,629 parents and 4,271 siblings were diagnosed with cancer. Relative Risks (RR) of cancer in first degree family members were calculated by using multivariable Cox regression analyses. We also calculated false-positive reporting probabilities. Significant concordant familial clustering was observed for stomach (RR(father) = 1.89, RR(parent) = 1.66, RR(sister) = 3.33, RR(sibling) = 2.38, RR(1st degree) = 1.69), colon/rectum (RR(father) = 1.82, RR(mother) = 1.83, RR(parent) = 1.88, RR(1st degree) = 1.56), lung (RR(brother) = 1.50) and breast cancer (RR(mother) = 1.65, RR(sister) = 1.72, RR(1st degree) = 1.72) with low false-positive reporting probabilities. Significant discordant familial clustering has been observed for combinations of pancreas-colon/rectum (RR(mother) = 2.42, RR(parent) = 1.89, RR(1st degree) = 1.73), larynx-lung (RR(father) = 3.35, RR(parent) = 2.84, RR(1st degree) = 2.30), lung-oesophagus (RR(sibling) = 3.49), breast-bladder (RR(father) = 2.79, RR(parent) = 2.61), endometrium-stomach (RR(mother) = 2.32), ovarium-oesophagus (RR(1stdegree) = 4.19), prostate-colon/rectum (RR(parent) = 1.46) and bladder-larynx/pharynx (RR(father) = 2.49) cancer, although false-positive reporting probabilities were higher for these associations. Familial clustering of cancer occurs at most sites but is generally modest. Some observed discordant familial clustering is surprising but should be interpreted with caution as their prior probability is low.

Since hyperinsulinemia is implicated in the development of colorectal cancer, determinants of serum insulin levels, like the glycemic load and the glycemic index of the diet, could influence cancer risk. Our objective was to evaluate whether a diet with a high glycemic load or glycemic index is associated with increased colorectal cancer risk. In the Netherlands Cohort Study, 120,852 subjects completed a food frequency questionnaire in 1986. After 11.3 years of follow-up, 1,225 colon and 418 rectal cancer cases were available for analysis. A case-cohort approach was used to estimate multivariate adjusted rate ratios and 95% confidence intervals for quintiles of energy-adjusted glycemic load and glycemic index. The RR for colorectal cancer comparing the highest versus the lowest quintile levels of glycemic load and glycemic index were 0.83 (95% CI: 0.64-1.08) and 0.81 (95% CI: 0.61-1.08) for men and 1.00 (95% CI: 0.73-1.36) and 1.20 (95% CI: 0.85-1.67) for women. In general, no clear associations with cancer subsites were observed. Glycemic load and glycemic index were borderline significantly associated with an increased risk of proximal colon cancer in women (p-trend = 0.06 and 0.08, respectively), however, these associations were attenuated after exclusion of the first 2 years of follow-up (p-trend = 0.165 and 0.254, respectively). In men, glycemic index was associated with a reduced risk of distal colon cancer (p-trend = 0.03). Overall, our findings do not support the hypothesis that a diet with a high glycemic load or index is associated with a higher risk of colorectal cancer. (c) 2007 Wiley-Liss, Inc.

Contains fulltext : 69987.pdf (Publisher’s version ) (Closed access) 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.

BACKGROUND: Acrylamide, a probable human carcinogen, was detected in various heat-treated carbohydrate-rich foods in 2002. The few epidemiologic studies done thus far have not shown a relationship with cancer. Our aim was to investigate the association between acrylamide intake and endometrial, ovarian, and breast cancer risk. METHODS: The Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline (1986), a random subcohort of 2,589 women was selected using a case cohort analysis approach for analysis. The acrylamide intake of subcohort members and cases was assessed with a food frequency questionnaire and was based on chemical analysis of all relevant Dutch foods. Subgroup analyses were done for never-smokers to eliminate the influence of smoking; an important source of acrylamide. RESULTS: After 11.3 years of follow-up, 327, 300, and 1,835 cases of endometrial, ovarian, and breast cancer, respectively, were documented. Compared with the lowest quintile of acrylamide intake (mean intake, 8.9 mug/day), multivariable-adjusted hazard rate ratios (HR) for endometrial, ovarian, and breast cancer in the highest quintile (mean intake, 40.2 mug/day) were 1.29 [95% confidence interval (95% CI), 0.81-2.07; P(trend) = 0.18], 1.78 (95% CI, 1.10-2.88; P(trend) = 0.02), and 0.93 (95% CI, 0.73-1.19; P(trend) = 0.79), respectively. For never-smokers, the corresponding HRs were 1.99 (95% CI, 1.12-3.52; P(trend) = 0.03), 2.22 (95% CI, 1.20-4.08; P(trend) = 0.01), and 1.10 (95% CI, 0.80-1.52; P(trend) = 0.55). CONCLUSIONS: We observed increased risks of postmenopausal endometrial and ovarian cancer with increasing dietary acrylamide intake, particularly among never-smokers. Risk of breast cancer was not associated with acrylamide intake. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2304-13). AD - Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, the Netherlands. JGF.Hogervorst@EPID.Unimaas.nl. FAU - Hogervorst, Janneke G AU - Hogervorst JG FAU - Schouten, Leo J AU - Schouten LJ FAU - Konings, Erik J AU - Konings EJ FAU - Goldbohm, R Alexandra AU - Goldbohm RA FAU - van den Brandt, Piet A AU - van den Brandt PA LA - eng PT - Journal Article PL - United States TA - Cancer Epidemiol Biomarkers Prev JT - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

High alcohol consumption is related to colorectal cancer (CRC). Our objective was to study associations between alcohol consumption and risk of CRC according to characteristics of aetiological pathways: the chromosomal instability (CIN) and the microsatellite instability (MIN) pathway. We classified CIN+ tumours (tumours with either a truncating APC mutation, an activating K-ras mutation or overexpression of p53), MIN+ tumours (tumours lacking hMLH1 expression) and CIN− /MIN− tumours (tumours without these defects). In the Netherlands Cohort Study on diet and cancer, 120 852 men and women, aged 55–69 years, completed a questionnaire on risk factors for cancer at baseline (1986). Case–cohort analyses were conducted using 573 CRC cases with complete data after 7·3 years of follow-up, excluding the first 2·3 years. Adjusted incidence rate ratios (RR) and 95 % confidence intervals (CI) were estimated. Compared with abstaining, alcohol consumption of ≥ 30 g/d was positively associated with the risk of CRC irrespective of genetic or molecular aberrations present, although statistical significance was not reached (RR 1·35 (95 % CI 0·9–2·0) for the CIN+ tumours, RR 1·59 (95 % CI 0·4–5·8) for the MIN+ tumours and RR 1.15 (95 % CI 0·5–2·7) for the CIN− /MIN− tumours). Beer, wine and liquor consumption were, independent of their alcoholic content, not consistently associated with the risk of CRC within the defined subgroups. In conclusion, our results indicate that a daily alcohol consumption of ≥ 30 g is associated with an increase in risk of CRC, independent of the presence or absence of the studied characteristics of different aetiological pathways.

Objective: To examine the association between alcohol consumption, cigarette smoking, and endometrial cancer. Methods: In 1986, the Netherlands Cohort Study was initiated. A self-administered questionnaire on dietary habits and other cancer risk factors was completed by 62,573 women. Follow-up for cancer was established by record linkage to the Netherlands Cancer Registry. Results: After 11.3-years of follow-up, 280 incident endometrial cancer cases were available for analyses. In multivariate analysis, the rate ratio (RR) for alcohol users versus non-users was 1.06 (95% Confidence Interval (95% CI)= 0.78-1.43). There were neither dose-dependent trends nor associations with different types of beverages. The RR for former and current smokers versus never-smokers was 0.83 (95% CI = 0.58-1.20) and 0.59 (95% CI = 0.40-0.88), respectively. These estimates did not change significantly when body mass index (BMI) and age at menopause were added to the models. Conclusions: There is no association between alcohol consumption and endometrial cancer. Current smoking is associated with a reduced risk of endometrial cancer. This association is neither mediated by BMI nor by age at menopause. © 2007 Springer Science+Business Media B.V.

Using data collected of a large population-based cohort study, we studied the association between anthropometric factors and the risk of pancreatic cancer. Furthermore, we investigated whether these associations differ among microscopically confirmed pancreatic cancer (MCPC) cases and non-MCPC (NMCPC) cases. The Netherlands Cohort Study on Diet and Cancer started in 1986 (120,852 men and women) and uses the case-cohort methodology. After 13.3 years of follow-up, 446 pancreatic cancer cases (of which 65% was microscopically confirmed) and 4,774 subcohort members were available for analysis. The multivariable incidence rate ratio of MCPC of men was 1.10 per increment of 1 kg·m−2 (95% confidence interval, 1.04-1.18). Women had a rate ratio of MCPC of 1.08 (95% confidence interval, 1.03-1.13). Obese men [body mass index (BMI) ≥30 kg·m−2] had a 2.6-fold increased risk of MCPC compared with men with BMI 23 to 25 kg·m−2. For women, this increase in risk was 1.7-fold. Change in BMI between age 20 years and baseline was also associated with MCPC in both men and women. In men and women, none of these associations were observed for NMCPC, with the exception of the increased risk for pancreatic cancer in obese men. We observed statistically significant associations between both BMI, gain in BMI, and pancreatic cancer risk. These associations are observed only in MCPC and not in NMCPC. If MCPC and NMCPC had been considered as one group, the reported associations would not have been detected. These findings stress the need to evaluate heterogeneity among pancreatic cancer cases in etiologic studies. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1449–54)

Background: In the last decades, the incidence of oesophageal and gastric cardia adenocarcinoma has increased rapidly in the Western world. We investigated the association between body mass index (BMI), height and risk of oesophageal and gastric cardia adenocarcinoma. Methods: The Netherlands Cohort Study was initiated in 1986. All participants (n = 120 852), aged 55-69 years, completed a self administered questionnaire. Cases were identified through annual record linkage with the Netherlands Cancer Registry. After 13.3 years of follow-up, excluding the first follow-up year, complete data from 4552 subcohort members, 133 oesophageal and 163 gastric cardia adenocarcinomas were available for case-cohort analyses. Incidence rate ratios (RRs) and corresponding 95% confidence intervals were estimated using Cox proportional hazard models. Results: The RRs (95% CI) of oesophageal adenocarcinoma were 1.40 (0.95 to 2.04) and 3.96 (2.27 to 6.88) for overweight (BMI 25.0-29.9 kg/m2) and obese subjects (BMI ≥ 30.0 kg/m2), respectively, compared to subjects with normal weight (BMI 20.0-24.9 kg/m2). For gastric cardia adenocarcinoma, these RRs were 1.32 (0.94 to 1.85) and 2.73 (1.56 to 4.79). Also change in BMI during adulthood was positively associated with the risk of oesophageal and gastric cardia adenocarcinoma (p trend 0.001 and 0.02, respectively), while no association was found with BMI in early adulthood (p trend 0.17 and 0.17, respectively). None of the tumour types investigated was significantly associated with height. Conclusions: These results confirm higher risks of oesophageal and gastric cardia adenocarcinoma with increasing BMI. This implies that the increasing prevalence of obesity may be one of the explanations for the rising incidence of oesophageal and gastric cardia adenocarcinoma in the Western world.

Contains fulltext : 51921.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. METHODS: After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. RESULTS: Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake