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Background: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk.Patients and methods: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models.Results: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI >= 35.0 kg/m(2) with 21-22.9 kg/m(2). When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI = 30.0 kg/m(2) at baseline compared with BMI = 110 cm with = 1.00 with = 1.90 m withConclusion: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Background Current risk models for renal cell carcinoma (RCC) based on clinicopathological factors are sub-optimal in accurately identifying high-risk patients. Here, we perform a head-to-head comparison of previously published DNA methylation markers and propose a potential prognostic model for clear cell RCC (ccRCC). Patients and methods Promoter methylation of PCDH8, BNC1, SCUBE3, GREM1, LAD1, NEFH, RASSF1A, GATA5, SFRP1, CDO1, and NEURL was determined by nested methylation-specific PCR. To identify clinically relevant methylated regions, The Cancer Genome Atlas (TCGA) was used to guide primer design. Formalin-fixed paraffin-embedded (FFPE) tissue samples from 336 non-metastatic ccRCC patients from the prospective Netherlands Cohort Study (NLCS) were used to develop a Cox proportional hazards model using stepwise backward elimination and bootstrapping to correct for optimism. For validation purposes, FFPE ccRCC tissue of 64 patients from the University Hospitals Leuven and a series of 232 cases from The Cancer Genome Atlas (TCGA) were used. Results Methylation of GREM1, GATA5, LAD1, NEFH, NEURL, and SFRP1 was associated with poor ccRCC-specific survival, independent of age, sex, tumor size, TNM stage or tumor grade. Moreover, the association between GREM1, NEFH, and NEURL methylation and outcome was shown to be dependent on the genomic region. A prognostic biomarker model containing GREM1, GATA5, LAD1, NEFH and NEURL methylation in combination with clinicopathological characteristics, performed better compared to the model with clinicopathological characteristics only (clinical model), in both the NLCS and the validation population with a c-statistic of 0.71 versus 0.65 and a c-statistic of 0.95 versus 0.86 consecutively. However, the biomarker model had limited added prognostic value in the TCGA series with a c-statistic of 0.76 versus 0.75 for the clinical model. Conclusion In this study we performed a head-to-head comparison of potential prognostic methylation markers for ccRCC using a novel approach to guide primers design which utilizes the optimal location for measuring DNA methylation. Using this approach, we identified five methylation markers that potentially show prognostic value in addition to currently known clinicopathological factors.

BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to

Purpose Evidence from cross-sectional studies suggests that higher levels of light-intensity physical activity (LPA) are associated with better health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. However, these associations have not been investigated in longitudinal studies that provide the opportunity to analyse how within-individual changes in LPA affect HRQoL. We investigated longitudinal associations of LPA with HRQoL outcomes in CRC survivors, from 6 weeks to 2 years post-treatment. Methods Data were used of a prospective cohort study among 325 stage I–III CRC survivors (67% men, mean age: 67 years), recruited between 2012 and 2016. Validated questionnaires were used to assess hours/week of LPA (SQUASH) and HRQoL outcomes (EORTC QLQ-C30, Checklist Individual Strength) at 6 weeks, and 6, 12 and 24 months post-treatment. We applied linear mixed regression to analyse longitudinal confounder-adjusted associations of LPA with HRQoL. Results We observed statistically significant longitudinal associations between more LPA and better global quality of life and physical, role and social functioning, and less fatigue over time. Intra-individual analysis showed that within-person increases in LPA (per 8 h/week) were related to improved HRQoL, including better global quality of life (β = 1.67, 95% CI 0.71; 2.63; total range scale: 0–100) and less fatigue (β = − 1.22, 95% CI − 2.37; − 0.07; scale: 20–140). Stratified analyses indicated stronger associations among participants below the median of moderate-to-vigorous physical activity (MVPA) at diagnosis. Conclusion Higher levels of LPA were longitudinally associated with better HRQoL and less fatigue in CRC survivors up to two years post-treatment. Further prospective studies using accelerometer data are necessary to inform development of interventions targeting LPA.

Background Nut intake has been associated with reduced cancer-related mortality and cancer risk. However, very few studies investigated the association between nut consumption and the risk of endometrial and ovarian cancer, with inconclusive results. We prospectively examined the relation between total nut, tree nut, peanut, and peanut butter intake and the risk of endometrial and ovarian cancer in the prospective Netherlands Cohort Study (NLCS). Methods In 1986, 62,573 women aged 55–69 years were included in the NLCS. At baseline, all participants filled in a questionnaire and a subcohort of 2,589 women was randomly selected. After 20.3 years of follow-up, 389 endometrial and 347 ovarian cancer cases with complete data were included in the analysis. Hazard ratios (HRs) were calculated in multivariable-adjusted Cox regression analyses, using a case-cohort approach. Results Compared to nonconsumers, the HRs (95% confidence intervals) for women consuming 10+ g total nuts/day were 1.23 (0.82–1.87) for endometrial cancer and 0.84 (0.57–1.24) for ovarian cancer. For tree nut, peanut, and peanut butter intake, also no significant relations with endometrial or ovarian cancer were observed. In the endometrial cancer analyses, significant interactions of total nut intake with body mass index and cigarette smoking status were found. Conclusion The results of this study suggest that intake of total nuts, tree nuts, peanuts, and peanut butter is not related to the risk of endometrial or ovarian cancer. The observed interactions in the endometrial cancer analyses, particularly by cigarette smoking status, require confirmation in other studies.

Sirtuin 1 (SIRT1) is an energy-sensing protein, which may affect tumorigenesis. We used SIRT1 variants as time-independent indicators of SIRT1 involvement in carcinogenesis and we studied two tagging SIRT1 variants in relation to colorectal cancer (CRC) risk. We also evaluated known energy balance-related CRC risk factors within SIRT1 genotype strata. The Netherlands Cohort Study includes 120,852 individuals and has 20.3 years follow-up (case-cohort: nsubcohort = 5000; nCRC cases = 4667). At baseline, participants self-reported weight, weight at age 20, height, trouser/skirt size reflecting waist circumference, physical activity, and early life energy restriction. SIRT1 rs12778366 and rs10997870 were genotyped in toenail DNA available for ~75% of the cohort. Sex- and subsite-specific Cox hazard ratios (HRs) showed that the rs12778366 CC versus TT genotype decreased CRC and colon cancer risks in women (HRCRC = 0.53, 95% confidence interval: 0.30–0.94) but not men. Multiplicative interactions were observed between SIRT1 variants and energy balance-related factors in relation to CRC endpoints, but the direction of associations was not always conform expectation nor specific to one genotype stratum. In conclusion, these results support SIRT1 involvement in colon cancer development in women. No conclusions could be made regarding a modifying effect of SIRT1 variants on associations between energy balance-related factors and CRC risk.

Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity, and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in the Netherlands Cohort Study (NLCS). Participants (n=120 852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19, and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12, and 90, >60-90

Background:Prostate cancer is the most commonly diagnosed cancer in men in Europe and the United States. Numerous studies have indicated genetics to have a major role in the aetiology of this disease; as much as 42% of the risk may be explained by heritable factors. Genome-wide association studies have detected an association between prostate cancer and chromosome 8p21-23. In this study, we analysed eight microsatellite (MS) markers in that region in order to confirm previous results and narrow down the location of candidate prostate cancer genes.Methods:292 cases and 278 controls were selected from the Netherlands Cohort Study (NLCS). The following MSs were used in the analyses: D8S136, D8S1734, D8S1742, D8S261, D8S262, D8S351, D8S511 and D8S520. Associations were evaluated using a χ 2 test and logistic regression. We checked for any effects on the association by tumour stage.Results:Associations that were found confirmed previous research that pointed to the 8p21-23 region. Two MSs: D8S136 (odds ratio (OR), 0.69; P=4.00 × 10 -28), and D8S520 (OR, 0.80; P=3.37 × 10 -11), were consistently and strongly related with prostate cancer. Genotype analysis showed an additive effect for D8S136 (P-trend=6.22 × 10 -03) and D8S520 (P-trend=2.62 × 10 -22), suggesting an increased risk for people with a short number of repeats on both alleles at those markers.Conclusions:This study provides strong evidence that the 8p21-23 region is likely to harbour prostate cancer genes.© 2013 Macmillan Publishers Limited All rights reserved. Chemicals/CAS: lipoprotein lipase, 83137-80-8, 9004-02-8

Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.

BACKGROUND/OBJECTIVES: The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets. SUBJECTS/METHODS: The Netherlands Cohort Study-Meat Investigation Cohort (NLCS-MIC)-is an analytical cohort of 11 082 individuals including 1133 self-reported vegetarians (aged 55-69 years at baseline). At baseline (1986), subjects completed a questionnaire on dietary habits and other risk factors for cancer and were classified into vegetarians (n = 691), pescetarians (n = 389), 1 day per week (n = 1388), 2-5 days per week (n = 2965) and 6-7 days per week meat consumers (n = 5649). RESULTS: After 20.3 years of follow-up, 279 lung, 312 postmenopausal breast and 399 prostate cancer cases (including 136 advanced) were available for analyses. After adjustment for confounding variables, we found no statistically significant association between meat consumption groups and the risk of lung cancer. As well, no significant associations were observed for postmenopausal breast and overall prostate cancer. After adjustment for confounders, individuals consuming meat 1 day per week were at a 75% increased risk of advanced prostate cancer compared with 6-7 days per week meat consumers (95% CI 1.03-2.97). CONCLUSIONS: Vegetarians, pescetarians and 1 day per week meat consumers did not have a reduced risk of lung, postmenopausal breast and overall prostate cancer compared with individuals consuming meat on a daily basis after taking confounders into account.

Introduction To study the properties of a screening instrument in predicting long-term sickness absence among employees with depressive complaints. Methods Employees at high risk of future sickness absence were selected by the screening instrument Balansmeter (BM). Depressive complaints were assessed with the depression scale of the Hospital Anxiety and Depression Scale. The total study population consisted of 7,401 employees. Sickness absence was assessed objectively and analyzed at 12 and 18 months of follow-up using company registers on certified sick leave. Results The relative risk (RR) for long-term sickness absence, for employees at high risk versus not at high risk, was 3.26 (95% CI 2.54-4.22) in men and 2.55 (1.98-3.35) in women, when the BM was applied in the total study population. The RR of long-term sickness absence of employees with depressive complaints compared with employees without depressive complaints was 3.13 (2.41-4.09) in men and 2.45 (2.00-3.00) in women. The RR of long-term sickness absence for the BM applied in employees with depressive complaints was 5.23 in men and 3.87 in women. When the BM with a cut-off point with a higher sensitivity was applied in employees with depressive complaints, the RR for long-term sickness absence was 4.88 in men and 3.80 in women. Conclusions The screening instrument Balansmeter is able to predict long-term sickness absence within employees with depressive complaints. The total prediction of long-term sickness absence proved better in employees with depressive complaints compared with employees of a general working population.

Ovarian cancer is a highly lethal disease. Many researchers have, therefore, attempted to identify high risk populations. In this perspective, numerous genetic association studies have been performed to discover common ovarian cancer susceptibility variants. Accordingly, there is an increasing need to synthesize the evidence in order to identify true associations. A comprehensive and systematic assessment of all available data on genetic susceptibility to sporadic ovarian cancer was carried out. The evidence of statistically significant findings was evaluated based on the number of positive replications, the ratio of positive and negative studies, and the false-positive report probability (FPRP). The authors reviewed three genome-wide association studies (GWAS) and 147 candidate gene studies, published from 1990 to October 2010, including around 1100 genetic variants in more than 200 candidate genes and 20 intergenic regions. Genetic variants with the strongest evidence for an association with ovarian cancer include the rs2854344 in the RB1 gene and SNPs on chromosomes 9p22.2, 8q24, 2q31, and 19p13. Promising genetic pathways for ovarian cancer include the cell cycle, DNA repair, sex steroid hormone and oncogenic pathway. Concluding, this review shows that many genetic association studies have been performed, but only a few genetic variants show strong evidence for an association with ovarian cancer. More research is needed to elucidate causal genetic variants, taking into consideration gene-gene and gene-environment interactions, combined effects of common and rare variants, and differences between histological subtypes of this cancer.

Within the Netherlands Cohort Study (1986), we examined associations between alcohol consumption, the alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer (CRC). After a follow-up period of 7.3 years, 594 CRC cases with information on genotype and baseline alcohol intake were available for analyses. Adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of >/=30g of alcohol per day with the ADH1C*2/*2 genotype were associated-although not statistically significant-with an increased risk of CRC relative to abstainers with the ADH1C*1/*1 genotype (RR: 1.91, 95% CI: 0.68, 5.34). The risk estimate in this exposure group increased slightly when compared with light drinkers of >/=0.5-.05). In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of >/=30g of alcohol per day were associated-although not statistically significant-with an increased risk of CRC relative to abstainers (RR: 1.38, 95% CI: 0.80, 2.38). This risk estimate for high-level drinkers became stronger when compared with light drinkers (RR: 1.74, 95% CI: 1.01, 2.99). As main effect of genotype, we observed that the ADH1C*2/*2 genotype was associated with a 42% increase in risk of CRC when compared with the ADH1C*1/*1 genotype. In conclusion, both genotype and alcohol consumption were associated with an increased risk of CRC. Owing to limited statistical power, we found no apparent evidence for the ADH1C genotype as effect modifier of the relationship between alcohol intake and CRC. Nevertheless, the interaction deserves further investigation in larger genetic epidemiologic studies.

To cite this article: Thijs C, Muller A, Rist L, Kummeling I, Snijders BEP, Huber M, van Ree R, Simoes-Wust AP, Dagnelie PC, van den Brandt PA. Fatty acids in breast milk and development of atopic eczema and allergic sensitisation in infancy. Allergy 2011; 66: 58–67. Abstract Background: One of the explanations for the increasing prevalence of atopic diseases is a relative low perinatal supply of n-3 fatty acids. However, this does not explain the protective effects of whole-fat dairy products or high levels of transfatty acids in breast milk, observed in some studies. We evaluated the role of perinatal supply of fatty acids in the early development of atopic eczema and allergic sensitisation. Methods: Fatty acids, including n-3 long-chain polyunsaturated fatty acids (LCPs) as well as ruminant fatty acids (rumenic acid, cis-9,trans-11-C18:2 conjugated linoleic acid; and vaccenic acid, trans-11-C18:1), were determined in breast milk sampled at 1 month postpartum from 310 mother–infant pairs in the KOALA Birth Cohort Study, the Netherlands. Children were followed for atopic outcomes until 2 years of age. Results: Higher concentrations of n-3 LCPs as well as ruminant fatty acids were associated with lower risk of (1) parent-reported eczema, (2) atopic dermatitis (UK Working Party criteria), and (3) sensitisation at age 1 year (as revealed by specific serum IgE levels to cow’s milk, hen’s egg and/or peanut). In multivariable logistic regression analysis, the inverse associations between ruminant fatty acid concentrations in breast milk and atopic outcomes were found to be independent from n-3 LCPs. Conclusions: The results confirm a protective role of preformed n-3 LCPs in the development of atopic disease. Moreover, this is the first study in humans confirming results from animal studies of protective effects of ruminant fatty acids against the development of atopic manifestations.

Objective To investigate the association between selenium and the risk of Barrett’s esophagus (BE), the precursor lesion of esophageal adenocarcinoma. Methods Data from the prospective Netherlands Cohort Study were used. This cohort study was initiated in 1986, when 120,852 subjects aged 55–69 years completed a questionnaire on dietary habits and lifestyle, and provided toenail clippings for the determination of baseline selenium status. After 16.3 years of follow-up, 253 BE cases (identified through linkage with the nationwide Dutch pathology registry) and 2,039 subcohort members were available for case–cohort analysis. Cox proportional hazards models were used to calculate incidence rate ratios (RR). Results The multivariable-adjusted RR for the highest versus the lowest quartile of toenail selenium was 1.06 (95% CI 0.71–1.57). No dose–response trend was seen (p trend = 0.99). No association was found in subgroups defined by sex, smoking status, body mass index (BMI), or intake of antioxidants. For BE cases that later progressed to high-grade dysplasia or adenocarcinoma, the RR for a selenium level above the median vs. below the median was 0.64 (95% CI 0.24–1.76). Conclusions In this large prospective cohort study, we found no evidence of an association between selenium and risk of BE. Electronic supplementary material The online version of this article (doi:10.1007/s10552-010-9651-1) contains supplementary material, which is available to authorized users.

Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian cancer among postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. Information on reproductive history and exogenous hormone use was obtained through a self-administered questionnaire at baseline in 1986. After 16.3 years of follow-up, 375 cases and 2,331 subcohort members were available for case-cohort analysis. Ovarian cancer risk was reduced for parous women, with increasing parity, and for hysterectomized women. Moreover, the authors found evidence that oral contraceptive use is protective against ovarian cancer, even when initiated at an older age. In addition, a reduced risk was observed for each year reduction in age at natural menopause and per year reduction in total menstrual life span. A small increased risk was observed with prolonged time to pregnancy, but no difference was found between ever-married nulliparous women and never-married nulliparous women. Moreover, no associations were observed for age at first birth, age at menarche, age at first and last use of oral contraceptives, and use of hormone replacement therapy.

Introduction In developed countries, the rising number of obese- and/or physically inactive individuals might negatively impact human lifespan. The aim of this study was to quantity the association between body size and non-occupational physical activity, and the chance of reaching longevity (defined as 90 years of age), in men and women separately. Methods For this study, data from the oldest birth cohort (1916–17) of the Netherlands Cohort Study (NLCS) was used. Participants (n = 7807) completed a baseline questionnaire in 1986 (at age 68–70). Follow-up for vital status information until the age of 90 years (2006–07) was > 99.9% complete. Multivariable-adjusted Cox regression analyses were based on 5479 participants with complete exposure and co-variable data to calculate risk ratios (RR) of reaching longevity. Results In women, increasing height was positively associated with reaching longevity [RR: 1.05; 95% confidence interval (CI): 1.00–1.09 per 5 cm increment]. Significantly inverse associations were observed between reaching longevity and BMI at baseline (≥ 30 vs. 18.5– Conclusion Body size at the age of 68–70 years showed significant associations with the chance of reaching longevity in women, but not in men. Increasing levels of non-occupational physical activity were significantly associated with an increased chance of reaching longevity in both sexes, but evidence for a non-linear relationship was found in women.

Background/Objectives: Acrylamide, a probable human carcinogen, was detected in various heat-treated foods such as French fries and potato crisps. Recently, positive associations have been found between dietary acrylamide intakes, as estimated with a food frequency questionnaire using an acrylamide database, and cancer risk in some epidemiological studies. As acrylamide levels vary considerably within the same type of foods, a validation study was performed to investigate whether use of an acrylamide food database containing calculated mean acrylamide content, based on extensive sampling and chemical analysis of Dutch foods (several samples per food), can classify subjects with respect to true acrylamide intake. Subjects/Methods: We used the data from a 24-h duplicate diet study. The acrylamide content of 39 Dutch 24-h duplicate diets collected in 2004 was estimated using the mean acrylamide levels of foods available from the database and the menu list, on which the participants of the duplicate diet study had listed the amounts of individual foods and drinks in household units. Next, the acrylamide content of the total duplicate diets was analytically measured and correlated to the estimated acrylamide contents. Results: The Spearman's correlation coefficient between chemically determined acrylamide content and the calculated acrylamide content of the duplicate diets was 0.82 (P

Objective: Alcohol consumption and cigarette smoking may be differentially associated with oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). However, because this was based on retrospective studies, these hypotheses were examined in a prospective cohort. Methods: The prospective Netherlands Cohort Study consists of 120 852 participants who completed a baseline questionnaire on diet and other cancer risk factors in 1986. After 16.3 years of follow-up, 107 OSCC, 145 OAC, 164 GCA and 491 GNCA cases were available for analysis using Cox proportional hazards models and the case-cohort approach. Results: The multivariable adjusted incidence rate ratio (RR) for OSCC was 4.61 (95% CI 2.24 to 9.50) for ≥30 g ethanol/day compared with abstainers (p trend 15 g/day of ethanol was 8.05 (95% CI 3.89 to 16.60; p interaction = 0.65), when compared with never smokers who consumed

Aberrant DNA methylation affects carcinogenesis of colorectal cancer. Folate metabolizing enzymes may influence the bioavailability of methyl groups, whereas DNA and histone methyltransferases are involved in epigenetic regulation of gene expression. We studied associations of genetic variants of folate metabolizing enzymes (MTHFR, MTR, and MTRR), DNA methyltransferase DNMT3b, and histone methyltransferases (EHMT1, EHMT2, and PRDM2), with colorectal cancers, with or without the CpG island methylator phenotype (CIMP), MLH1 hypermethylation, or microsatellite instability. Incidence rate ratios were calculated in case-cohort analyses, with common homozygotes as reference, among 659 cases and 1,736 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852). Men with the MTHFR 677TT genotype were at decreased colorectal cancer risk (incidence rate ratio, 0.49; P = 0.01), but the T allele was associated with increased risk in women (incidence rate ratio, 1.39; P = 0.02). The MTR 2756GG genotype was associated with increased colorectal cancer risk (incidence rate ratio, 1.58; P = 0.04), and inverse associations were observed among women carrying DNMT3b C→T (rs406193; incidence rate ratio, 0.72; P = 0.04) or EHMT2 G→A (rs535586; incidence rate ratio, 0.76; P = 0.05) polymorphisms. Although significantly correlated (P < 0.001), only 41.5% and 33.3% of CIMP tumors harbored MLH1 hypermethylation or microsatellite instability, respectively. We observed inverse associations between MTR A2756G and CIMP among men (incidence rate ratio, 0.58; P = 0.04), and between MTRR A66G and MLH1 hypermethylation among women (incidence rate ratio, 0.55; P = 0.02). In conclusion, MTHFR, MTR, DNMT3b, and EHMT2 polymorphisms are associated with colorectal cancer, and rare variants of MTR and MTRR may reduce promoter hypermethylation. The incomplete overlap between CIMP, MLH1 hypermethylation, and microsatellite instability indicates that these related “methylation phenotypes” may not be similar and should be investigated separately. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3086–96)

Objectives: To assess male lung cancer risks for industrial sectors in the Netherlands and to estimate the proportion of lung cancer attributed to working in specific industrial sectors. Methods: Associations were studied among men aged 55-69 years (n = 58 279) from the prospective Netherlands Cohort Study. 1920 incident lung cancer cases were available after 11.3 years of follow-up. Based on a case-cohort design, and using Cox proportional hazards models, risks were estimated for blue collar workers in 26 industrial sectors. Results: Adjustment for individual smoking habits affected risk estimates for some sectors, but adjustment for fruit/vegetables and alcohol intake did not. Adjusted for confounders, an increased risk of lung cancer was observed for employment for ≥15 years in blue collar jobs in the "electronics and optical instruments" industry (rate ratio (RR) 1.99; 95% CI 1.18 to 3.35), "construction and homebuilding business" (RR 1.64; 95% CI 1.21 to 2.22) and "railway company" (RR 2.40; 95% CI 1.00 to 5.73). The attributable fraction for working for ≥15 years in these three industries was 5%. In three other sectors there was a statistically non-significant elevated RR of >1.5. Conclusions: Male lung cancer risk is increased in several industrial sectors. Approximately 2000 lung cancer cases between 1986 and 1997 in the 55-69-year-old age group in the Netherlands may be attributable to working for ≥15 years in the three sectors with increased risk. In addition, estimates for occupational lung cancer risks for sectors may be biased if no individual information is available on smoking habits.

Objectives: To assess the association of whole-grain and (cereal) fibre intake with body mass index (BMI) and with the risk of being overweight (BMI ≥ 25) or obese (BMI ≥ 30 kg m-2). Subjects: A total of 2078 men and 2159 women, aged 55-69 years, were included in the analysis, after exclusion of subjects with diagnosed cancer or deceased within 1 year after baseline or with missing dietary information. Results: We found an inverse association between whole-grain consumption and BMI and risk of overweight and obesity in men as well as women. The association in men was stronger than in women; the risk of being obese as compared to normal weight was 10% (95% CI: 2-16%) and 4% (95% CI: 1-7%) lower for each additional gram of (dry) grain consumption in men and women, respectively. Fibre and cereal fibre intake were inversely associated with BMI in men only. Associations were similar after exclusion of likely under- and overreporters of energy. A retrospective analysis of baseline fibre intake and weight gain after the age of 20 years also showed a slight inverse association. Conclusions: Whole-grain consumption may protect against becoming overweight or obese; however, the cross-sectional design of the study does not allow conclusions about the causality of the association.

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed.

Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases and 2216 subcohort members were available for analysis. No association was seen between consumption of milk yoghurt, cheese or fermented dairy products and ovarian cancer risk. The multivariable adjusted relative risk of epithelial ovarian cancer for women in the highest compared to the lowest quintile of intake of lactose or dairy fat was 0.93 (95% confidence interval (CI) = 0.60-1.45; Ptrend = 0.32) and 1.53 (95% CI = 1.00-2.36; Ptrend = 0.11), respectively. Lactose or dairy fat intakes were not associated with serous ovarian cancer risk. Our results do not support an association between consumption of dairy products or lactose intake and ovarian cancer. © 2006 Cancer Research. Chemicals / CAS: lactose, 10039-26-6, 16984-38-6, 63-42-3, 64044-51-5; Dietary Fats; Lactose, 63-42-3

Summary Background The rise in atopic diseases has been linked to disturbances in the intestinal microbiota composition. Objective The purpose of this study was to investigate the intestinal microbiota composition in infants in whom atopic (IgE-associated) eczema was or was not developing, using a molecular fingerprinting technique. Methods Within a prospective birth cohort study, fecal samples have been collected at the infant's age of 1 month. Within the context of this cohort, we conducted a nested case–control study comparing fecal samples of 26 infants who became sensitized and developed eczema within the first year of life with 52 non-sensitized non-eczematous infants. The composition of the fecal samples was examined using PCR combined with denaturing gradient gel electrophoresis. Using real-time PCR, total bacterial counts and bifidobacterial counts were enumerated. Results Neither total bacterial profiles nor the type and proportion of bifidobacteria in the feces were associated with the development of atopic eczema. The similarity of bacterial profiles was low; mean similarity was approximately 33% in both infants with or without atopic eczema. The prevalence of one specific band in total bacterial profiles was significantly higher in infants with atopic eczema compared with controls (96% vs. 71%, P=0.01). Identification of this band revealed that it represented Escherichia coli. Conclusion Although no association was found between the development of IgE-associated eczema and the dominant gut microbiota as a whole or with the bifdobacterial microbiota, the association with E. coli indicates that differences in gut microbiota do precede the development of atopy.

Contains fulltext : 58090.pdf (Publisher’s version ) (Closed access) BACKGROUND: In the Netherlands in 1997, 43% of patients with newly diagnosed lung cancer were over 70. Large age-specific differences in treatment exist. We examined whether age, comorbidity, performance status and pulmonary function influenced treatment. PATIENTS AND METHods: Data on patients with newly diagnosed non-small cell lung cancer (N = 803) were obtained: comorbidity, performance status, pulmonary function (FEV1) and initial treatment. Age-specific differences in treatment according to the guidelines were examined. Odds ratios were calculated by means of logistic regression analyses. RESULTS: 82% with stage I or II disease received treatment according to the guidelines; this applied to 48% with stage IIIA disease and to 54% with stage IIIB disease. For all stages, this proportion decreased with increasing age. In stage IV disease, 36% did not receive any treatment; this applied to 52% of the elderly patients (75+ years). Multivariate analyses showed associations between comorbidity and treatment choice, but none with performance status. Age of 75+ years appeared to be the most important factor for not receiving treatment according to guidelines. CONCLUSION: A substantial proportion of elderly patients with non-small cell lung cancer did not receive standard treatment. Performance status and comorbidity seldom formed the underlying reason. Calendar rather than biological age seemed to play the most important role in choice of treatment for patients with non-small cell lung cancer.

We reviewed 37 prospective cohort and four intervention studies on potential dietary risk factors for prostate cancer, published between 1966 and September 2003. Some studies were limited by small size, crude measurement of dietary exposure and limited control for confounders. Intervention and prospective cohort studies support a protective role against prostate cancer for selenium, and possibly for vitamin E, pulses and tomatoes/lycopene. Overall consumption of meat, eggs, vegetables, fruit, coffee, tea, carotenoids and vitamins A, C and D was not consistently related to prostate cancer risk. Intervention studies also indicate that supplementation with beta-carotene does not lower prostate cancer risk, except possibly in men with low beta-carotene status at baseline. For specific types of meat, alcoholic drinks, dairy products, fat and anthropometric measures, most cohort studies suggest either an increased risk or no relation with prostate cancer. For calcium, two cohort studies suggest an increased risk at very high calcium intakes (>2000 mg/day). In conclusion, prospective studies are consistent with a protective role for selenium, and possibly vitamin E, pulses and tomatoes/lycopene, in the aetiology of prostate cancer. Studies are inconclusive on the role of meat, dairy products, fat, vegetables, fruits, alcohol and anthropometric measures, whereas a very high calcium intake appears to be positively associated with prostate cancer risk.

In this paper the association between smoking history, beverage consumption, diet and bladder cancer incidence is systematically reviewed. A rating system has been used to summarise the level of scientific evidence (i.e. convincing, probable, possible, and no evidence) and the level of association (i.e. substantially increased, (RR> or =2.5), moderately increased (1.5< or =RR

Behavioral approaches to treating patients following lumbar disc surgery are becoming increasingly popular. The treatment method is based on the assumption that pain and pain disability are not only influenced by somatic pathology, if found, but also by psychological and social factors. A recent study high-lighted the effectiveness of cognitive-behavioral interventions, as compared to no treatment, for chronic low back patients. However, to the authors' knowledge, there is no randomized controlled trial that evaluates a behavioral program for patients following lumbar disc surgery. The purpose of this study was to assess the effectiveness of a behavioral graded activity (BGA) program compared to usual care (UC) in physiotherapy following first-time lumbar disc surgery. The BGA program was a patient-tailored intervention based upon operant therapy. The essence of the BGA is to teach patients that it is safe to increase activity levels. The study was designed as a randomized controlled trial. Assessments were carried out before and after treatment by an observer blinded to treatment allocation. Patients suffering residual symptoms restricting their activities of daily living and/or work at the 6 weeks post-surgery consultation by the neurosurgeon were included. The exclusion criteria were: complications during surgery, any relevant underlying pathology, and any contraindication to physiotherapy or the BGA program. Primary outcome measures were the patient's Global Perceived Effect and the functional status. Secondary measures were: fear of movement, viewing pain as extremely threatening, pain, severity of the main complaint, range of motion, and relapses. Physiotherapists in the BGA group received proper training. Between November 1997 and December 1999, 105 patients were randomized; 53 into the UC group and 52 into the BGA group. The unadjusted analysis shows a 19.3% (95% CI: 0.1 to 38.5) statistically significant difference to the advantage of the UC group on Global Perceived Effect. This result, however, is not robust, as the adjusted analyses reveal a difference of 15.7% (95% CI: -3.9 to 35.2), which is not statistically significant. For all other outcome measures there were no statistically significant or clinically relevant differences between the two intervention groups. In general, the physiotherapists' compliance with the BGA program was satisfactory, although not all treatments, either in the BGA or the UC group, were delivered exactly as planned, resulting in less contrast between the two interventions than had been planned for. There was one re-operation in each group. The BGA program was not more effective than UC in patients following first-time lumbar disc surgery. For Global Perceived Effect there was a borderline statistically significant difference to the advantage of the UC group. On functional status and all other outcome measures there were no relevant differences between interventions. The number of re-operations was negligible, indicating that it is safe to exercise after first-time disc surgery.

Aims: To determine whether psychosocial work environment and indicators of health problems are prospectively related to incident long term sickness absence in employees who visited the occupational physician (OP) and/or general practitioner (GP) in relation to work. Methods: The baseline measurement (May 1998) of the Maastricht Cohort Study, a prospective cohort study among 45 companies and organisations, was used to select employees at work who indicated having visited the OP and/or GP in relation to work. Self report questionnaires were used to measure indicators of health problems (presence of at least one long term disease, likeliness of having a mental illness, fatigue) and psychosocial work environment (job demands, decision latitude, social support, job satisfaction) as predictors of subsequent sickness absence. Sickness absence data regarding total numbers of sickness absence days were obtained from the companies and occupational health services during an 18 month period (between 1 July 1998 and 31 December 1999). Complete data were available from 1271 employees. Results: After adjustment for demographics and the other predictors, presence of at least one long term disease (OR 2.36; 95% CI 1.29 to 4.29) and lower level of decision latitude (OR 1.69; 95% CI 1.22 to 2.38) were the strongest predictors for sickness absence of at least one month. A higher likelihood of having a mental illness, a higher level of fatigue, a lower level of social support at work, and low job satisfaction were also significant predictors for long term sickness absence, but their effect was less strong. Conclusion: In detecting employees at work but at risk for long term sickness absence, OPs and GPs should take into account not only influence of the psychosocial work environment in general and level of decision latitude in particular, but also influence of indicators of health problems, especially in the form of long term diseases.

Objective: Many case-control studies have reported that salt and cured meat intake are positively, and refrigerator use is inversely, associated with stomach cancer risk. In the current prospective study these associations were evaluated. Methods: The Netherlands Cohort Study consisted of 120,852 men and women ages 55-69 years at baseline in 1986. Salt exposure was measured by calculating mean daily sodium intake (dietary salt) from 150 food items and by specific salt questions. After 6.3 years of follow-up, 282 incident stomach cancer cases were available for analyses. Case-cohort analyses were based on the 282 cases and 3123 subcohort members. Results: In multivariate analyses adjusted for age, sex, smoking, education, stomach disorders, history of stomach cancer in the family, rate ratios (RR) for increasing quintiles of energy-adjusted intake of dietary salt were 1.00, 1.49, 1.03, 1.54 and 1.18, respectively (p trend = 0.43). An inverse association was found between stomach cancer and salt added at the hot meal (p trend = 0.04). For salt added to home-made soup, use of salt at the table, salt preference and duration of refrigerator use, no associations were observed. Positive associations were found for bacon (RR highest/lowest intake = 1.33; 95% CI = 1.03-1.71) and other sliced cold meat (RR highest/lowest intake = 1.29; 95% CI = 0.96-1.72), but not for smoked sausage, total cold meats, rashers/bacon, boiled ham and smoked beef/pork loin roll. Separate analyses among subjects with self-reported stomach disorders revealed higher RR of stomach cancer for dietary salt and several types of cured meat. Conclusion: The present findings suggest that intake of dietary salt and several types of cured meat were weakly positively associated with stomach cancer risk.

Background. Prolonged fatigue has recently attracted attention in occupational (mental) health research since it may lead to sickness absenteeism and work disability. To date, little is known about the role of psychosocial work characteristics in the aetiology of fatigue. In this study we examined prospectively a wide range of psychosocial work characteristics as possible risk factors for the onset of fatigue and psychological distress in the working population.Methods. This study is based on 8833 employees, participating in the Maastricht Cohort Study of ‘Fatigue at Work’. A wide range of psychosocial work characteristics, measured at baseline, was used to predict the onset of fatigue and psychological distress 1 year later. Fatigue was measured with the Checklist Individual Strength; the General Health Questionnaire was used to measure psychological distress.Results. The cumulative incidence of fatigue during 1 year follow-up was 9·7% (N = 492) in men, and 13·5% (N = 241) in women. Psychological demands at work as well as physical and emotional demands increased the risk for fatigue in men, whereas decision latitude in men and co-worker social support in women were protective against fatigue. These prospective associations remained significant after adjustments for potential confounders and baseline fatigue. As regards psychological distress, no association was found with decision latitude, while conflicts at work increased the risk of psychological distress.Conclusions. Psychosocial work characteristics were significant predictors for the onset of fatigue in the working population. The prospective associations suggest some differential effects in the aetiology of fatigue and psychological distress. Good interpersonal relationships at work and high decision authority were demonstrated to be relevant aspects that should be targeted for prevention.

Epidemiologic studies directly contribute data on risk (or benefit) in humans as the investigated species, and in the full food intake range normally encountered by humans. This paper starts with introducing the epidemiologic approach, followed by a discussion of perceived differences between toxicological and epidemiologic risk assessment. Areas of contribution of epidemiology to the risk assessment process are identified, and ideas for tailoring epidemiologic studies to the risk assessment procedures are suggested, dealing with data collection, analyses and reporting of both existing and new epidemiologic studies. The dietary habits and subsequent disease occurrence of over three million people are currently under observation worldwide in cohort studies, offering great potential for use in risk assessment. The use of biomarkers and data on genetic susceptibility are discussed. The paper describes a scheme to classify epidemiologic studies for use in risk assessment, and deals with combining evidence from multiple studies. Using a matrix approach, the potential contribution to each of the steps in the risk assessment process is evaluated for categories of food substances. The contribution to risk assessment of specific food substances depends on the quality of the exposure information. Strengths and weaknesses are summarized. It is concluded that epidemiology can contribute significantly to hazard identification, hazard characterisation and exposure assessment.

Item does not contain fulltext This study examined the prevalence of common infections among employees in different work schedules. Self-administered questionnaire data from the Maastricht Cohort Study on "Fatigue at Work" (n = 12,140) were used. Job title was used as a matching variable between day and shift workers to control for their different work environment. We used a multilevel analysis of a two-level structure, in which the individual employees (level 1) were nested within job titles (level 2), adjusted for demographics, longstanding disease, health behavior, work-related factors, fatigue and sleep quality. Results from the multilevel analyses showed that, compared to day work, shift work was associated with a higher risk for common infections, with the highest risk in three-shift workers. Compared to day work, shift work was further associated with differences in health, health behavior, sleep, fatigue and perceived job characteristics, factors that may influence the occurrence of infections and should be taken into account in future studies as well.

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 icecream 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

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 120852 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 center dot 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 center dot 66, 95% CI 0 center dot 43, 1 center dot 01), raw (HR 0 center dot 63, 95% CI 0 center dot 40, 0 center dot 99), raw leafy (HR 0 center dot 55, 95% CI 0 center dot 36, 0 center dot 86) and Brassica (HR 0 center dot 64, 95% CI 0 center dot 41, 1 center dot 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 center dot 50, 95% CI 0 center dot 25, 0 center dot 99) and positively associated with it in women (HR 3 center dot 77, 95% CI 1 center dot 68, 8 center dot 45) (P for interaction=0 center dot 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.

Am J Clin Nutr 2001 Jul;74(1):141-8 Related Articles, Books, LinkOut Comment in: Am J Clin Nutr. 2001 Jul;74(1):4-5. Plant sterol intakes and colorectal cancer risk in the Netherlands Cohort Study on Diet and Cancer.Normen AL, Brants HA, Voorrips LE, Andersson HA, van den Brandt PA, Goldbohm RA.Department of Clinical Nutrition, Goteborg University, Goteborg, Sweden.BACKGROUND: Plant sterols in vegetable foods might prevent colorectal cancer. OBJECTIVE: The objective was to study plant sterol intakes in relation to colorectal cancer risk in an epidemiologic study. DESIGN: The study was performed within the framework of the Netherlands Cohort Study on Diet and Cancer in 120852 subjects who completed a baseline questionnaire in 1986. After 6.3 y of follow-up, 620 colon and 344 rectal cancer cases were detected. A case-cohort approach was used to calculate confounder-adjusted rate ratios (RRs) and their 95% CIs for quintiles of plant sterol intake. RESULTS: The total mean (+/-SD) intake of campesterol, stigmasterol, beta-sitosterol, campestanol, and beta-sitostanol was 285 +/- 97 mg/d. Major contributors to plant sterol intake were bread (38%), vegetable fats (26%), and fruit and vegetables (21%). For men, there was no clear association between intake of any of the plant sterols and colon cancer risk when age, smoking, alcohol use, family history of colorectal cancer, education level, and cholecystectomy were controlled for. Adjustment for energy did not alter the result. For rectal cancer, adjustment for energy resulted in positive associations between risk and campesterol and stigmasterol intakes. For women, there was no clear association between intake of any of the plant sterols and colorectal cancer risk. CONCLUSION: A high dietary intake of plant sterols was not associated with a lower risk of colon and rectal cancers in the Netherlands Cohort Study on Diet and Cancer.

Objectives: Coffee, tea, and fluid consumption have been thought to influence bladder cancer incidence. In a large prospective study, these associations were investigated. Methods: In 1986, cohort members (55-69 years) completed a questionnaire on cancer risk factors. Follow-up was established by linkage to cancer registries until 1992. The multivariable case-cohort analysis was based on 569 bladder cancer cases and 3123 subcohort members. Results: The incidence rate ratios (RR) for men consuming < 2 cups of coffee/day was 0.89 (95% CI 0.51-1.5) using the median consumption category (4-< 5 cups/day) as reference. This RR increased to 1.3 (95% CI 0.94-1.9) for men consuming ≥7 cups/day, although no clear dose-response association was found. The RRs decreased from 1.2 (95% CI 0.56-2.7) for women consuming

Am J Epidemiol 2001 Sep 15;154(6):530-7 Related Articles, Books, LinkOut Energy restriction in childhood and adolescence and risk of prostate cancer: results from the Netherlands Cohort Study.Dirx MJ, van den Brandt PA, Goldbohm RA, Lumey LH.Department of Epidemiology, Faculty of Health Sciences, Maastricht University, Maastricht, the Netherlands. MJM.Dirx@epid.unimaas.nlThis study investigated the association between prostate cancer risk and energy restriction during childhood. The authors examined the hypothesis among 58,279 men aged 55-69 years enrolled in the Netherlands Cohort Study on Diet and Cancer. Information on diet and risk factors was collected by questionnaire in 1986. Additional information was collected on residence during the Dutch Hunger Winter (1944-1945) and the World War II years (1940-1944) and father's employment status during the economic depression of 1932-1940, used as indicators of exposure. A case-cohort approach was used. After 7.3 years of follow-up (through December 1993), 903 prostate cancer cases were available for analysis. Analyses were carried out for all prostate cancer cases. The prostate cancer rate ratio for men who had lived in a western Netherlands city in 1944-1945 was 1.15 (95% confidence interval (CI): 0.80, 1.31), and the rate ratio for men who had lived in a western rural area in 1944-1945 was 1.30 (95% CI: 0.97, 1.73). Residence during the war years (1940-1944) and father's employment in 1932-1940 showed no relation to prostate cancer risk. In subgroup analyses in which exposure before, during, and after the adolescent growth spurt was evaluated, the same pattern as that of the overall data was shown. The authors found no evidence for the hypothesis that energy restriction early in life decreases prostate cancer risk later in life.

BACKGROUND Cancer incidence and mortality rates rarely are studied in people age > 85 years. Usually, patients ages 65 years, 75 years, and 85 years of age are combined into 1 group because of small numbers. The number of people age ≥ 85 years in the Netherlands increased from 99,000 in 1976 to 203,000 in 1995 (an increase of 105%). The growth of the total population in this period was only 13%. This study addressed cancer incidence and mortality rates among the very elderly in the Netherlands. METHODS Cancer mortality data (1976–1995) and population data were obtained from Statistics Netherlands, whereas cancer incidence data (1989–1995) were provided by the Netherlands Cancer Registry. Cancer incidence and mortality rates were calculated and trends in cancer mortality were studied. RESULTS Total cancer incidence rates were highest in the age group 85–94 years, in men and women (3466/100,000 person-years and 1604/100,000 person-years, respectively). Prostate carcinoma was the most frequent cancer in men ages 85–94 years, followed by colorectal carcinoma. In women ages 85–94 years, colorectal carcinoma was most frequent, closely followed by breast carcinoma. In the 95+ years age group squamous cell skin carcinoma was the most frequent cancer in both men and women, followed by prostate carcinoma in men and breast carcinoma in women. Cancer mortality rates increased with increasing age to nearly 3700/100,000 person-years in men age 95+ years and 2500/100,000 person-years in women age 95+ years. In men, lung carcinoma was the most frequent cancer-related cause of death in patients age ≤ 85 years, whereas in older men this applied to prostate carcinoma. In women, breast carcinoma was the most frequent cancer-related cause of death in all age groups > 55 years. Cancer as a cause of death became less prominent with increasing age. Over the period 1991–1995, 42% of deaths in men ages 55–64 years were attributed to cancer versus 52% of deaths in women (total population); these proportions in the 95+ years age group were 11% and 7%, respectively. CONCLUSIONS Peak incidence rates of major cancers were found in the very elderly population in the Netherlands. Different trends in age specific mortality rates of individual cancer sites were found, with stable rates in the middle age groups and increasing rates in the oldest age groups. This may reflect a real increase caused for instance by changes in mortality from other diseases and/or an artifactual increase caused by increased cancer detection rates in the (very) elderly. Cancer 2000;89:1121–33. © 2000 American Cancer Society.

Background In many western countries an increase in incidence of adenocarcinoma of the oesophagus and/or gastric cardia have been reported. The aim of this study was to describe and compare trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in several areas of Europe, 1968-1995, using Eurocim (a database of cancer incidence and mortality data from 95 European cancer registries). Methods Time-trends in age-standardized incidence rates of adenocarcinomas of the oesophagus and gastric cardia are described in 11 population-based cancer registries from 10 countries in North, South, East, West and Central Europe, 1968-1995. The statistical significance of the time-trends in incidence was assessed using Poisson regression analysis. Results An increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was observed in Northern Europe (Denmark), Southern Europe (Italy, Varese), Eastern Europe (Slovakia) and Western Europe (England and Wales, Scotland). In Central Europe (Switzerland, Basel) and in the cancer registries of Iceland (Northern Europe), France, Bas-Rhin and Calvados, Southern Ireland, and the Netherlands, Eindhoven (Western Europe) no rise in incidence was observed. The increase in incidence of adenocarcinomas of the oesophagus and gastric cardia was accompanied by a decrease in incidence of both adenocarcinomas and non-adenocarcinomas of the non-cardia part of the stomach in almost all of the 11 cancer registries studied. Increased histological verification of tumours of the oesophagus and stomach and improvement in precision of histological diagnosis may partly explain the increase in incidence of adenocarcinomas in some registries. Conclusions This study, using Eurocim data, supports the findings from other time-trend studies of population-based cancer registries in western countries.

BACKGROUND. Numerous components of fruit and vegetables are considered to decrease the risk of gastric carcinoma. In the current prospective study, the authors examined the association between the intake of vitamins, carotenoids, and dietary fiber and vitamin supplement use and the incidence rate of gastric carcinoma. METHODS. The Netherlands Cohort Study began in 1986 with 120,852 men and women ages 55-69 years. Data regarding diet and other covariates were collected by means of a self-administered questionnaire. After 6.3 years of follow-up, data regarding 282 incident cases of gastric carcinoma and 3123 subcohort members were available for case-cohort analyses. RESULTS. In analyses adjusted for age, gender, smoking history, education, stomach disorders, and family history of gastric carcinoma, an inverse association with vitamin C intake (relative risk [RR] for highest vs. lowest intake category, 0.7; 95% confidence interval [95% CI], 0.5-1.0) was observed, with a borderline significant trend across three intake categories (P = 0.06). After the exclusion of cases diagnosed in the first and second follow-up years, the RR was 0.9 (95% CI, 0.6-1.2; P trend = 0.44). Intake of retinol and β-carotene were associated positively with gastric carcinoma risk with highest versus lowest quintile RRs of 1.6 (95% CI, 1.0-2.5; P trend = 0.02) and 1.6 (95% CI, 1.0-2.6; P trend = 0.13), respectively, after the exclusion of first-year and second-year cases. Intake of folate, vitamin E, α-carotene, lutein plus zeaxanthin, β-cryptoxanthin, lycopene, and dietary fiber was not associated with gastric carcinoma. Patients who used vitamin A-containing supplements had a lower risk of gastric carcinoma than nonusers (RR = 0.4; 95% CI, 0.2-0.9). CONCLUSIONS. No clear inverse associations were found between the intake of vitamins, carotenoids, and dietary fiber and the risk of gastric carcinoma after adjustment for confounding variables and the exclusion of first-year and second-year cases. (C) 2000 American Cancer Society. Chemicals/CAS: Anticarcinogenic Agents; Ascorbic Acid, 50-81-7; Carotenoids, 36-88-4; Vitamin A, 11103-57-4; Vitamin E, 1406-18-4; Vitamins

Objective: The purpose was to study the association between vegetable and fruit consumption and lung cancer incidence using 1074 cases after 6.3 years of follow-up in the Netherlands Cohort Study. Methods: Dietary intake was assessed using a 150-item food-frequency questionnaire. Multivariate models were used including age, sex, family history of lung cancer, highest educational level attained, and smoking history. Results: Statistically significant inverse associations were found with total vegetables and most vegetable groups. Rate ratios (RRs) based on consumption frequency showed the strongest effect of vegetables from the Brassica group (RR 0.5, 95% confidence interval (95% CI) 0.3-0.9, for consumption ≥ 3 times per week versus ≤ once a month). RR of highest versus lowest quintile of total vegetable consumption was 0.7 (95% CI 0.5-1.0, p-trend 0.001). Statistically significant inverse associations were found for all fruits listed in the questionnaire. RRs for quintiles of total fruit intake were 1.0, 0.7, 0.6, 0.6 and 0.8 respectively (p-trend < 0.0001). Protective effects of fruits and vegetables were stronger in current than in former smokers, and weaker for adenocarcinomas than for other types of tumors. Conclusions: Inverse associations with lung cancer are found for both vegetable and fruit intake, but no specific type of vegetable or fruit seems to be particularly responsible.

The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies.

Department of Epidemiology, Maastricht University, The Netherlands.We investigated the risk of prostate cancer in relation to a family history of prostate cancer in 58,279 men ages 55-69 years. We found 704 incident cases after 6.3 years of follow-up. Rate ratios and 95% confidence intervals for having an affected vs nonaffected father and brother were, respectively 1.44 (0.80-2.58) and 5.57 (1.61-19.26). We found no evidence for an increasing risk with an increasing percentage of affected family members. The associations we observed were stronger for cases diagnosed before age 70 compared with cases diagnosed after age 70 and for advanced compared with localized tumors.

Objectives: To examine alcohol consumption in relation to prostate cancer incidence in the Netherlands Cohort Study.

Objectives: Recent narrative reviews have concluded that there is no support for an association between alcohol consumption and urinary tract cancer. Many individual studies, however, have reported positive associations, although rarely statistically significant. The purpose of this meta-analysis is to summarize and quantify this relationship with more statistical power and to perform a sensitivity analysis on the study characteristics.

Department of Epidemiology, Maastricht University, The Netherlands.The association between vegetable and fruit consumption and stomach cancer risk was investigated in the Netherlands Cohort Study among 120,852 men and women aged 55-69 years at the start in September 1986. Analyses were based on 282 incident stomach cancer cases after 6.3 years of follow-up. Age- and sex-adjusted rate ratios of stomach cancer in increasing quintiles of combined vegetable and fruit consumption were 1.00, 0.70, 0.65, 0.76, and 0.64 (p trend = 0.04). Multivariate analysis resulted in rate ratios that were somewhat closer to one (p trend = 0.14). Furthermore, inverse associations for total vegetables, pulses, raw leafy vegetables, total fruit, citrus fruit, and apples and pears that were observed in crude analyses became weaker or disappeared in multivariate analyses. Total vegetable, but not fruit, consumption was significantly lower in cases diagnosed in the first follow-up year. In analyses limited to first year cases (resembling a case-control study), rate ratios for increasing tertiles of total vegetable consumption were 1.00, 0.17, and 0.18 (p trend = 0.0001), which may indicate the presence of information bias in case-control studies. This prospective study suggests that vegetable and fruit consumption was not clearly associated with stomach cancer risk in the Dutch population. The findings of this study are comparable with findings of other cohort studies, but they do not support the findings of case-control studies.

Maastricht University, Department of Epidemiology, The Netherlands.STUDY OBJECTIVE: To study the association between socioeconomic status (SES) and stomach cancer incidence (cardia and non-cardia) and the role of lifestyle factors in explaining this association. DESIGN: Prospective cohort study on diet and cancer that started in 1986. Data were collected by means of a self administered questionnaire. SETTING: Population originating from 204 municipalities in the Netherlands. PARTICIPANTS: 58,279 men aged 55-69 years. After 4.3 years of follow up, 162 incident stomach cancer cases were detected (49 cardia and 113 non-cardia cases). MAIN RESULTS AND CONCLUSIONS: After adjustment for age, a lower overall stomach cancer risk was found for men with the highest attained level of education (RR highest/lowest level = 0.54, 95% CI 0.33, 0.89, trend, p = 0.02). This association became less strong after additional adjustment for smoking, intake of vitamin C, beta carotene, alcohol and coffee, family history of stomach cancer, and history of stomach disorders (RR = 0.61, 95% CI 0.34, 1.07, trend, p = 0.11). No clear association was found between occupation based SES indicators and stomach cancer risk. Analyses per subsite of stomach cancer revealed that for people with the highest level of education the age adjusted rate ratio for cardia cancer changed from 0.37 (95% CI = 0.13, 1.00) to 0.60 (95% CI = 0.19, 1.87) after additional adjustment for lifestyle variables, whereas the rate ratio for non-cardia cancer (RR = 0.59, 95% CI 0.33, 1.05) did not change after additional adjustment.