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Objective: The aim of this study was to develop and validate a comprehensive food frequency questionnaire (FFQ) for The Maastricht Study, a population-based prospective cohort study in Maastricht, The Netherlands., Methods: Item selection for the FFQ was based on explained variation and contribution to intake of energy and 24 nutrients. For validation, the FFQ was completed by 135 participants (25-70 y of age) of the Nutrition Questionnaires plus study. Per person, on average 2.8 (range 1-5) telephone-based 24-h dietary recalls (24HRs), two 24-h urinary samples, and one blood sample were available. Validity of 54 nutrients and 22 food groups was assessed by ranking agreement, correlation coefficients, attenuation factors, and ultimately deattenuated correlation coefficients (validity coefficients)., Results: Median correlation coefficients for energy and macronutrients, micronutrients, and food groups were 0.45, 0.36, and 0.38, respectively. Median deattenuated correlation coefficients were 0.53 for energy and macronutrients, 0.45 for micronutrients, and 0.64 for food groups, being >0.50 for 18 of 22 macronutrients, 16 of 30 micronutrients and >0.50 for 17 of 22 food groups. The FFQ underestimated protein and potassium intake compared with 24-h urinary nitrogen and potassium excretion by -18% and -2%, respectively. Correlation coefficients ranged from 0.50 and 0.55 for (fatty) fish intake and plasma eicosapentaenoic acid and docosahexaenoic acid, and from 0.26 to 0.42 between fruit and vegetable intake and plasma carotenoids., Conclusion: Overall, the validity of the 253-item Maastricht FFQ was satisfactory. The comprehensiveness of this FFQ make it well suited for use in The Maastricht Study and similar populations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: In the Netherlands, various FFQs have been administered in large cohort studies, which hampers comparison and pooling of dietary data. The present study aimed to describe the development of a standardized Dutch FFQ, FFQ-NL1.0, and assess its compatibility with existing Dutch FFQs., Design: Dutch FFQTOOLTM was used to develop the FFQ-NL1.0 by selecting food items with the largest contributions to total intake and explained variance in intake of energy and thirty-nine nutrients in adults aged 25-69 years from the Dutch National Food Consumption Survey (DNFCS) 2007-2010. Compatibility with the Maastricht-FFQ, Wageningen-FFQ and EPICNL-FFQ was assessed by comparing the number of food items, the covered energy and nutrient intake, and the covered variance in intake., Results: FFQ-NL1.0 comprised 160 food items, v. 253, 183 and 154 food items for the Maastricht-FFQ, Wageningen-FFQ and EPICNL-FFQ, respectively. FFQ-NL1.0 covered ≥85 % of energy and all nutrients reported in the DNFCS. Covered variance in intake ranged from 57 to 99 % for energy and macronutrients, and from 45 to 93 % for micronutrients. Differences between FFQ-NL1.0 and the other FFQs in covered nutrient intake and covered variance in intake were <5 % for energy and all macronutrients. For micronutrients, differences between FFQ-NL and other FFQs in covered level of intake were <15 %, but differences in covered variance were much larger, the maximum difference being 36 %., Conclusions: The FFQ-NL1.0 was compatible with other FFQs regarding energy and macronutrient intake. However, compatibility for covered variance of intake was limited for some of the micronutrients. If implemented in existing cohorts, it is advised to administer the old and the new FFQ in combination to derive calibration factors.

A standardised, national, 160-item FFQ, the FFQ-NL 1.0, was recently developed for Dutch epidemiological studies. The objective was to validate the FFQ-NL 1.0 against multiple 24-h recalls (24hR) and recovery and concentration biomarkers. The FFQ-NL 1.0 was filled out by 383 participants (25-69 years) from the Nutrition Questionnaires plus study. For each participant, one to two urinary and blood samples and one to five (mean 2·7) telephone-based 24hR were available. Group-level bias, correlation coefficients, attenuation factors, de-attenuated correlation coefficients and ranking agreement were assessed. Compared with the 24hR, the FFQ-NL 1.0 estimated the intake of energy and macronutrients well. However, it underestimated intakes of SFA and trans-fatty acids and alcohol and overestimated intakes of most vitamins by >5 %. The median correlation coefficient was 0·39 for energy and macronutrients, 0·30 for micronutrients and 0·30 for food groups. The FFQ underestimated protein intake by an average of 16 % and K by 5 %, relative to their urinary recovery biomarkers. Attenuation factors were 0·44 and 0·46 for protein and K, respectively. Correlation coefficients were 0·43-0·47 between (fatty) fish intake and plasma EPA and DHA and 0·24-0·43 between fruit and vegetable intakes and plasma carotenoids. In conclusion, the overall validity of the newly developed FFQ-NL 1.0 was acceptable to good. The FFQ-NL 1.0 is well suited for future use within Dutch cohort studies among adults.

Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk., Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort., Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs., Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41)., Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat., (© 2016 American Society for Nutrition.)

Background: Dietary patterns have been associated with the incidence or mortality of individual non-communicable diseases, but their association with disease burden has received little attention., Objective: The aim of our study was to relate dietary patterns to health expectancy using quality-adjusted life years (QALYs) as outcome parameter., Methods: Data from the EPIC-NL study were used, a prospective cohort study of 33,066 healthy men and women aged 20-70 years at recruitment. A lifestyle questionnaire and a validated food frequency questionnaire were administered at study entry (1993-1997). Five dietary patterns were studied: three a priori patterns (the modified Mediterranean Diet Score (mMDS), the WHO-based Healthy Diet Indicator (HDI) and the Dutch Healthy Diet index (DHD-index)) and two a posteriori data-based patterns. QALYs were used as a summary health measure for healthy life expectancy, combining a person's life expectancy with a weight reflecting loss of quality of life associated with having chronic diseases., Results: The mean QALYs of the participants were 74.9 (standard deviation 4.4). A higher mMDS and HDI were associated with a longer life in good health. Participants who had a high mMDS score (6-9) had 0.17 [95% CI, 0.05; 0.30] more QALYs than participants with a low score (0-3), equivalent to two months longer life in good health. Participants with a high HDI score also had more QALYs (0.15 [95% CI, 0.03; 0.27]) than participants with a low HDI score., Conclusion: A Mediterranean-type diet and the Healthy Diet Indicator were associated with approximately 2months longer life in good health., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine the association between adherence to the Dutch Guidelines for a Healthy Diet created by the Dutch Health Council in 2006 and overall and smoking-related cancer incidence., Design: Prospective cohort study., Setting: Adherence to the guidelines, which includes one recommendation on physical activity and nine on diet, was measured using an adapted version of the Dutch Healthy Diet (DHD) index. The score ranged from 0 to 90 with a higher score indicating greater adherence to the guidelines. We estimated the hazard ratios (HR) and 95 % confidence intervals for the association between the DHD index (in tertiles and per 20-point increment) at baseline and cancer incidence at follow-up., Subjects: We studied 35 608 men and women aged 20-70 years recruited into the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study during 1993-1997., Results: After an average follow-up of 12·7 years, 3027 cancer cases were documented. We found no significant association between the DHD index (tertile 3 v. tertile 1) and overall (HR = 0·97; 95 % CI 0·88, 1·07) and smoking-related cancer incidence (HR = 0·89; 95 % CI 0·76, 1·06) after adjustment for relevant confounders. Excluding the components physical activity or alcohol from the score did not change the results. None of the individual components of the DHD index was significantly associated with cancer incidence., Conclusions: In the present study, participants with a high adherence to the Dutch Guidelines for a Healthy Diet were not at lower risk of overall or smoking-related cancer. This does not exclude that other components not included in the DHD index may be associated with overall cancer risk.

Background: Food choices influence health status, but also have a great impact on the environment. The production of animal-derived foods has a high environmental burden, whereas the burden of refined carbohydrates, vegetables and fruit is low. The aim of this study was to investigate the associations of greenhouse gas emission (GHGE) and land use of usual diet with mortality risk, and to estimate the effect of a modelled meat substitution scenario on health and the environment., Methods: The usual diet of 40011 subjects in the EPIC-NL cohort was assessed using a food frequency questionnaire. GHGE and land use of food products were based on life cycle analysis. Cox proportional hazard ratios (HR) were calculated to determine relative mortality risk. In the modelled meat-substitution scenario, one-third (35 gram) of the usual daily meat intake (105 gram) was substituted by other foods., Results: During a follow-up of 15.9 years, 2563 deaths were registered. GHGE and land use of the usual diet were not associated with all-cause or with cause-specific mortality. Highest vs. lowest quartile of GHGE and land use adjusted hazard ratios for all-cause mortality were respectively 1.00 (95% CI: 0.86-1.17) and 1.05 (95% CI: 0.89-1.23). Modelled substitution of 35 g/d of meat with vegetables, fruit-nuts-seeds, pasta-rice-couscous, or fish significantly increased survival rates (6-19%), reduced GHGE (4-11%), and land use (10-12%)., Conclusions: There were no significant associations observed between dietary-derived GHGE and land use and mortality in this Dutch cohort. However, the scenario-study showed that substitution of meat with other major food groups was associated with a lower mortality risk and a reduced environmental burden. Especially when vegetables, fruit-nuts-seeds, fish, or pasta-rice-couscous replaced meat.

Background: The role of differences in diet on the relationship between socioeconomic factors and cardiovascular diseases remains unclear. We studied the contribution of diet and other lifestyle factors to the explanation of socioeconomic inequalities in cardiovascular diseases., Methods: We prospectively examined the incidence of coronary heart disease (CHD) and stroke events amongst 33,106 adults of the EPIC-NL cohort. Education and employment status indicated socioeconomic status. We used Cox proportional models to estimate hazard ratios ((HR (95% confidence intervals)) for the association of socioeconomic factors with CHD and stroke and the contribution of diet and lifestyle., Results: During 12 years of follow-up, 1617 cases of CHD and 531 cases of stroke occurred. The risks of CHD and stroke were higher in lowest (HR=1.98 (1.67;2.35); HR=1.55 (1.15;2.10)) and lower (HR=1.50 (1.29;1.75); HR=1.42 (1.08;1.86)) educated groups than in the highest. Unemployed and retired subjects more often suffered from CHD (HR=1.37 (1.19;1.58); HR=1.20 (1.05;1.37), respectively), but not from stroke, than the employed. Diet and lifestyle, mainly smoking and alcohol, explained more than 70% of the educational differences in CHD and stroke and 65% of employment status variation in CHD. Diet explained more than other lifestyle factors of educational and employment status differences in CHD and stroke (36% to 67% vs. 9% to 27%)., Conclusion: The socioeconomic distribution of diet, smoking and alcohol consumption largely explained the inequalities in CHD and stroke in the Netherlands. These findings need to be considered when developing policies to reduce socioeconomic inequalities in cardiovascular diseases., (© 2013.)

Background: A healthy dietary pattern defined by international recommendations of the World Health Organisation (WHO) has been shown to reduce overall mortality risk. It is unknown whether this healthy dietary pattern is associated with overall cancer incidence., Design: In total 35,355 men and women within the Dutch European Prospective Investigation into Cancer and Nutrition-cohort were followed for cancer occurrence. Diet was assessed through a validated food-frequency questionnaire. We computed a dietary score for all participants based on the seven WHO dietary guidelines for the prevention of chronic diseases (Healthy Diet Indicator (HDI)). We used the existing HDI score based on the 1990 WHO guidelines, and adapted it to meet with the 2002 WHO guidelines. Multivariate-adjusted Cox proportional hazards analysis was used to examine the association between adherence to the HDI and subsequent overall cancer risk., Results: A number of 3,007 new cancers were identified during a mean follow-up of 12.7 years. Adherence to the HDI was not associated with a reduced overall cancer risk. The hazard ratio (HR) of overall cancer associated with a one-point increment of the HDI was 0.96 (95% CI 0.89-1.03) in men, and 1.00 (95% CI 0.96-1.04) in women. Adherence to the HDI was not associated with smoking-related cancer ((HR men: 0.94 (95% CI 0.84-1.04); HR women: 1.00 (95% CI 0.94-1.07)), or alcohol-related cancer ((HR men: 1.02 (95% CI 0.87-1.20); HR women: 1.03 (95% CI 0.98-1.08))., Conclusions: Greater adherence to the WHO's Healthy Diet Indicator, a dietary pattern for prevention of chronic diseases, was not associated with reduced overall, smoking-related or alcohol-related cancer risk in men or women.

Background: Several studies have suggested an increased risk of bladder cancer among hairdressers, who are occupationally exposed to hair dyes. There has also been concern about a possible increased risk of bladder cancer among users of hair dyes. However, the association between personal hair dye use and bladder cancer risk remains inconclusive., Objective: In this study, we examined associations between personal use of permanent and temporary hair dyes and bladder cancer risk in a population-based case-control study involving 1,385 cases (n = 246 women) and 4,754 controls (n = 2,587 women)., Methods: Participants filled out a questionnaire with regard to history of personal hair dye use and risk factors for bladder cancer. Unconditional logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI), adjusted for age, smoking status, duration of smoking and intensity of smoking., Results: Analyses were restricted to women as less than 5 % of all men in the study ever used hair dyes. About 50 % of the women ever used hair dyes. Use of temporary hair dyes (OR, 0.77; 95 % CI, 0.58-1.02) or use of permanent hair dyes (OR, 0.87; 95 % CI, 0.65-1.18) was not associated with bladder cancer risk. No clear association between hair dyes and bladder cancer risk was found when dye use was defined by type, duration or frequency of use, dye color, or extent of use. Also, results were similar for aggressive- and non-aggressive bladder cancer. Age, educational level, and smoking status did not modify the association between hair dye use and bladder cancer risk., Conclusions: The present study does not support an association between personal hair dye use and bladder cancer risk. Also, various types of hair dye, intensity of exposure to hair dyes or dye color do not appear to be important factors for bladder cancer development.

Background: Obesity is related to many adverse health-related outcomes., Objective: We investigated whether changes in physical activity were related to less gain in either body weight or waist circumference (WC)., Design: The association between prospectively assessed physical activity and either body weight or WC was examined in 4944 participants of the Doetinchem Study (men and women aged between 26 and 66 y at baseline). Information on physical activity (derived from a validated physical activity index), body weight, and WC, measured according to standardized procedures, was collected at baseline and at the 5- and 10-y follow-ups., Results: Random mixed-effects models showed that a single measurement of physical activity was not clearly related to change in body weight and WC over a 5-y period. However, analyses of repeated measures showed that compared with those who maintained their activity level, those who increased their physical activity over a 5-y period had less gain in WC ( minus 0.35 cm; 95% CI: minus 0.65, minus 0.05 cm) and possibly in body weight ( minus 280 g; 95% CI: minus 620, 5 g). Most importantly, these effects were sustained (although not significantly) in the consecutive 5 y for WC ( minus 0.56 cm; 95% CI: minus 108, 0.04 cm) and for body weight ( minus 590 g; 95% CI: minus 1005, minus 130 g), which indicated that physical activity was truly a determinant of body size changes., Conclusions: An increase in physical activity was associated with a statistically significant lower gain in body weight and in WC, which was maintained during the following 5 y. These findings support the need for public health programs that promote physical activity.

Purpose: To investigate risk factors that may be linked to pancreatic cancer., Methods: We designed a multicenter population-based case-control (823 cases, 1679 control patients) study with data collection by using a common protocol and questionnaire. Participating centers were located in Australia, Canada, the Netherlands, and Poland., Results: After adjustment for confounding factors, a positive history of pancreatitis was associated with pancreatic cancer (odds ratio [OR], 4.68; 95% confidence interval [95% CI], 2.23-9.84). The risk was especially high in heavy smokers (OR, 15.4; 95% CI, 3.18-74.9). Patients with diabetes had an increased risk of developing pancreatic cancer (OR, 2.16; 95% CI, 1.60-2.91). The risk was highest in the first year after the development of diabetes (OR, 6.68; 95% CI, 3.56-12.6) and decreased over time. A history of allergy was associated with a reduced risk of pancreas cancer (OR, 0.64; 95% CI, 0.50-0.82)., Conclusions: Patients with newly diagnosed diabetes and patients with pancreatitis, particularly in heavy smokers, have an increased risk for developing pancreatic cancer. In addition to being risk factors, these conditions could be early manifestations of underlying pancreatic cancer. A history of allergy decreases the risk of pancreatic cancer., (2010 Elsevier Inc. All rights reserved.)

Objective: A retrospective cohort study was conducted in two chlorophenoxy herbicide manufacturing factories, producing mainly 2,4,5-trichlorophenoxyacetic acid (factory A) and 4-chloro-2-methylphenoxyacetic acid, 4-chloro-2-methylphenoxy propanoic acid and 2,4-dichlorophenoxyacetic acid (factory B). Previously, we have shown elevated risks for mortality and cancer mortality in this cohort. The purpose of the current, third follow-up, is to provide an updated assessment of cause-specific mortality for both factories., Methods: The study population was defined as all persons working in one of the two factories during 1955-1985 for factory A, or during 1965-1986 for factory B. Analyses were performed using Cox proportional hazard models, using attained age as the timescale. Exposure to phenoxy herbicides and dioxins was expected to be different for factory A and factory B and the factories were therefore analysed separately., Results: Previously reported increased risks for respiratory cancer, non-Hodgkin's lymphoma and ischaemic heart disease in factory A could not be confirmed in the present analysis. However, increased risks were observed for all cancers in both factory A (hazard ratio (HR) 1.31; 95% CI 0.86 to 2.01) and factory B (HR 1.54; 95% CI 1.00 to 2.37). Increased risks for urinary cancers (HR 4.2; 95% CI 0.99 to 17.89) and genital cancers (HR 2.93; 95% CI 0.61 to 14.15) were observed in factory A, consistent with earlier reported results in this population. More detailed analyses showed that this increased risk for urinary and genital cancers in exposed workers was not due to selection of healthy controls and could not be attributed to specific products or departments., Conclusion: The results of this study showed only slight increases in cancer mortality risk. The increased risk for urinary cancers is noteworthy, but could not be linked to a specific exposure and needs to be confirmed in similar cohorts.

Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis. The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospective study. Among more than 35,000 participants aged 20-59 years, 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up (1987-2003). Cohort members who were frequency-matched to the cases on age, sex, and study center were selected as controls (n = 387). Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors (highest quartile vs. lowest: for enterodiol, odds ratio = 1.11, 95% confidence interval: 0.56, 2.20 (p-trend = 0.75); for enterolactone, odds ratio = 1.70, 95% confidence interval: 0.88, 3.27 (p-trend = 0.15)). However, sex (p-interaction = 0.06) and body mass index (p-interaction < 0.01) modified the relation between plasma enterolactone and colorectal cancer risk; increased risks were observed among women and subjects with a high body mass index. The association between plasma enterodiol and colorectal cancer risk was modified by smoking status; risk was increased among current smokers (p-interaction < 0.01). These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer.

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies.

Background: The need to gain insight into prevailing eating patterns and their health effects is evident., Objective: This study aimed to identify dietary patterns and their relation to total mortality in older Dutch women., Design: A principal component analysis of 22 food groups was used to identify dietary patterns in 5427 women aged 60-69 y who were included in the Dutch European Prospective Investigation into Cancer and Nutrition-Elderly cohort (follow-up: approximately 8.2 y). Mortality ratios for 3 major principal components were assessed by using Cox proportional hazard analysis., Results: The most relevant principal components were a Mediterranean-like dietary pattern (high intakes of vegetable oils, pasta and rice, sauces, fish, and wine), a Traditional Dutch dinner dietary pattern (high intakes of meat, potatoes, vegetables, and alcoholic beverages), and a Healthy Traditional Dutch dietary pattern (healthy variant of the Traditional Dutch dinner dietary pattern; high intakes of vegetables, fruit, nonalcoholic drinks, dairy products, and potatoes). Differences in mean intakes between the highest and lowest tertiles of the 3 patterns were greatest for fruit, dairy products, potatoes, and alcoholic beverages. Consumption of Mediterranean foods, such as fish and oils, was relatively low overall. Two hundred seventy-seven deaths occurred in 44,667 person-years. Independent of age, education, and other lifestyle factors, only the Healthy Traditional dietary pattern score was associated with a lower mortality rate. Women in the highest tertile of this pattern experienced a 30% reduction in mortality risk., Conclusion: A Healthy Traditional Dutch diet, rather than a Mediterranean diet, appears beneficial for longevity and feasible for health promotion in older Dutch women. This diet is comparable with other reported healthy or prudent diets that have been shown to be protective against morbidity or mortality.

Aim: Prostaglandin G/H synthase 2 (PTGS2 or COX2) is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases (IBD). In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD., Methods: We have genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTGS2 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5' exonuclease assay (TaqMan). New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing., Results: Allele 5209G was weakly associated with Crohn's disease (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.03-2.57), and allele 8473T with ulcerative colitis (OR 1.50, 95%CI 1.00-2.27). The haplotype including both alleles showed a strong association with IBD (OR 13.15, 95%CI 3.17-116.15). This haplotype, while rare (-0.3%) in the general population, is found more frequently in the patients (3.5%)., Conclusion: Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.

Variants in the metabolic genes NAT1, NAT2, GSTM1 or GSTT1, may cause differences in individual detoxifying capacity of possible carcinogens. We examined the cumulative effect of putative at risk genotypes on breast cancer risk and we examined the extent to which these polymorphisms modify the association between smoking and breast cancer. A case cohort study was conducted in the DOM cohort with 676 breast cancer cases and a random sample of 669 individuals. No effect of the NAT1, NAT2 or GSTM1 genotypes on breast cancer risk was observed. However, women with GSTT1 null genotype had a 30% increased breast cancer risk compared to women with GSTT1 present (RR = 1.30 (95% confidence interval (CI) 1.04-1.64)). Smoking did not influence breast cancer risk nor did genetic variations in NAT1, NAT2 or GSTM1 in combination with smoking. Compared to women who never smoked with GSTT1 present, women with GSTT1 null genotype and who formerly smoked showed an increased breast cancer risk (RR = 2.55 (95% CI 1.10-5.90)), but current smokers who smoked 20 cigarettes or more per day did not (RR = 1.06 (95% CI 0.51-2.18)). Increasing numbers of putative at risk genotypes increased breast cancer risk in a dose dependent manner (p for trend 0.01). The risk was more than doubled in women with all four risk genotypes, RR = 2.45 (95% CI 1.24-4.86), compared to women with zero putative at risk genotypes. In conclusion, the results of this study suggest that presence of three or more putative at risk genotypes increases breast cancer risk.

Enterolignans (enterolactone and enterodiol) are phytoestrogens that are formed by the colonic microflora from plant lignans. They may reduce the risk of certain types of cancer and cardiovascular diseases. Initially, only secoisolariciresinol and matairesinol were considered to be enterolignan precursors, but recently, new precursors such as lariciresinol and pinoresinol were identified. We recently developed a lignan database including 4 major enterolignan precursors. We used this database to estimate lignan intake in a representative sample of Dutch men and women participating in the Dutch Food Consumption Survey, carried out in 1997-1998. Median total lignan intake among 4660 adults (19-97 y old) was 979 microg/d. Total lignan intake did not differ between men and women; thus, the lignan density of the diet was significantly higher (P < 0.001) in women than in men. Lignan intake was strongly skewed toward higher values (range 43-77584 microg/d, mean 1241 microg/d). Lariciresinol and pinoresinol contributed 75% to lignan intake, whereas secoisolariciresinol and matairesinol contributed only 25%. The major food sources of lignans were beverages (37%), vegetables (24%), nuts and seeds (14%), bread (9%), and fruits (7%). Lignan intake was significantly (P < 0.001) correlated with intake of dietary fiber (r = 0.46), folate (r = 0.39), and vitamin C (r = 0.44). Older persons, nonsmokers, vegetarians, and persons with a low BMI or a high socioeconomic status had higher lignan intakes than their counterparts. In brief, this study shows that the amount of enterolignan precursors in the diet has previously been largely underestimated.

Objective: Epidemiological studies suggest that individuals with elevated plasma concentrations of insulin-like growth factor (IGF-I) are at increased risk of developing cancer. We assessed whether dietary intake of total energy, protein, alcohol, phytoestrogens and related foods, and tomatoes and lycopene was associated with plasma levels of IGF-I and IGF binding proteins (IGFBPs) in Dutch women., Methods: A cross-sectional study was conducted in 224 premenopausal and 162 postmenopausal women, aged 49-69, participating in the Prospect-EPIC study in the Netherlands. Diet was assessed using a food frequency questionnaire., Results: In postmenopausal women, higher alcohol intake was associated with lower plasma IGFBP-1 concentrations (alcohol 1.4 to 20 g/day: 20% decrease in IGFBP-1; p = 0.04), and higher intake of plant lignans was associated with higher IGFBP-1 concentrations (plant lignans 0 to 1 mg/day: 59% increase in IGFBP-1; p =0.02). Higher soy intake was associated with higher plasma IGFBP-2 concentrations in premenopausal women (soy 0 to 2.5 g/day: 3% increase in IGFBP-2; p = 0.04). No independent associations of dietary factors with IGF-I or IGFBP-3 concentrations were observed. However, in premenopausal women alcohol intake was inversely associated with IGF-I and positively associated with IGFBP-3 after mutual adjustment., Conclusions: In this study population, with limited variation in dietary intake, total energy, protein, phytoestrogens and lycopene were not associated with IGF-I and IGFBP-3. Alcohol was inversely, and some measures of phytoestrogen intake were positively associated with plasma IGFBP-1 or -2 concentrations. The roles of IGFBP-1 and -2 in relation to IGF-I bioactivity and cancer deserve further investigation.

Background: The prevalence of adult coeliac disease in The Netherlands was studied in the Dutch Coeliac Disease Society and in blood donors but not in the general population. We therefore studied the prevalence of recognized and unrecognized coeliac disease in a large cohort, representative of the adult Dutch general population. Blood samples were available for anonymous research, as well as data on dietary habits, self-reported physical characteristics, health problems, quality of life and socio-economic circumstances., Methods: Subjects included 50,760 individuals who had previously participated in two large population-based studies on health status in relation to lifestyle factors. Recognized coeliac disease was studied in all subjects by identification of self-reported adherence to a gluten-free diet and subsequent confirmation of the diagnosis of coeliac disease. Unrecognized coeliac disease was studied in a random sample of 1440 out of the 50,760 subjects through serologic screening and human lymphocyte antigen (HLA) typing., Results: The prevalence of recognized coeliac disease was 0.016% (95% confidence interval 0.008-0.031) and of unrecognized coeliac disease 0.35% (95% confidence interval 0.15-0.81). Menarcheal age was higher in women with recognized coeliac disease than in women without coeliac disease., Conclusions: The prevalence of adult recognized coeliac disease in The Netherlands is one of the lowest in Europe, while the prevalence of unrecognized coeliac disease is comparable with that in other European countries. Adult coeliac disease is strongly under diagnosed in The Netherlands. The higher menarcheal age in women with recognized coeliac disease may be explained by diagnostic delay.

Objective: We studied whether polymorphisms in N-acetyltransferase 1 and 2 and Glutathione S-transferase M1 and T1 genes modify the association between meat consumption and breast cancer., Methods: A nested case control was conducted in a Dutch prospective cohort. Breast cancer cases (229) and controls (264) were frequency matched on age, town and menopausal status., Results: There is no relation between any type of meat consumption ( i.e., total meat, processed meat, fresh meat, red meat and white meat) and breast cancer risk. Neither presence of NAT1 or NAT2 rapid genotype, or GSTT1 null genotype, alone or in combination with meat consumption affects breast cancer risk. Absence of GSTM1 shows 46% increased breast cancer risk (OR = 1.46 (95% confidence interval, 95% CI = 1.02-2.09)). When stratifying according to combined 'GSTM1 genotype-meat consumption' categories, breast cancer risk is slightly increased with consumption of red meat both in women with genotype GSTM1 presence (OR = 1.49 and 1.75 for intermediate and high versus low consumption) and in GSTM1 null genotype (OR = 1.18 and 1.02). These increases are statistically not significant. In postmenopausal women a suggestion of an effect of red meat consumption is observed: effects are slightly stronger, although still not statistically significant and without a clear dose-response relation: OR = 1.79 (95% CI = 0.92-3.50) and 1.46 (1.46 (95% CI = 0.76-2.82) for intermediate and high compared to low red meat consumption respectively. Reliable evaluation of interaction is not possible due to the small number of cancers., Conclusion: GSTM1 null genotype increases breast cancer risk. Red meat consumption slightly increases breast cancer risk, but the relation is not statistically significant and GSTM1, NAT1, NAT2 and GSTT1 polymorphisms do not modify this relation., (Copyright 2004 Kluwer Academic Publishers)

N-acetyltransferase (NAT) 1 and 2 and glutathione S-transferase (GST) M1 and T1 are phase II enzymes that are important for activation and detoxification of carcinogenic heterocyclic and aromatic amines, as present in cigarette smoke. We studied whether genetic polymorphisms in these genes modifies the relationship between smoking and breast cancer. A nested case-control study was conducted among participants in a Dutch prospective cohort. Breast cancer cases (n=229) and controls (n=264) were frequency-matched on age, menopausal status and residence. Compared to never smoking, smoking 20 cigarettes or more per day increased breast cancer risk statistically significant only in postmenopausal women [odds ratio (OR)=2.17; 95% confidence interval (CI) 1.04-4.51]. Neither NAT1 slow genotype, or GSTT1 null genotype, alone or in combination with smoking, affected breast cancer risk. However, compared to individuals with rapid NAT2 genotype, women with the very slow acetylator genotype (NAT2*5), who smoked for 20 years showed an increased breast cancer risk (OR=2.29; 95% CI 1.06-4.95). Similarly, the presence of GSTM1 null genotype combined with high levels of cigarette smoking (OR=3.00; 95% CI 1.46-6.15) or long duration (OR=2.53; 95% CI 1.24-5.16), increased rates of breast cancer. The combined effect of GSTM1 null genotype and smoking high doses was most pronounced in postmenopausal women (OR=6.78; 95% CI 2.31-19.89). In conclusion, our results provide support for the view that women who smoke and who have a genetically determined reduced inactivation of carcinogens (GSTM1 null genotype or slow NAT2 genotype (especially very slow NAT2 genotype)) are at increased risk of breast cancer.

Purpose: To describe the cross-sectional association of counts of total and subtypes of leukocytes, platelets, and selected characteristics of red blood cells with intensity of cigarette smoking and smoking cessation., Methods: The study population consisted of 16,254 men and women 20-70 years of age who participated in the Dutch European Prospective Investigation into Cancer and nutrition (EPIC) subcohort, 1995-1997. Linear regression analysis was performed, for both sexes separately, to study the relation between various measurements of smoking habits and hematologic characteristics., Results: Among current smokers, in both genders, packyears and daily number of cigarettes were associated with increased leukocytes (6-19%), lymphocytes (4-14%), monocytes (3-9%), neutrophils (7-24%), platelets (1-5%), mean corpuscular volume (0.4-2%), hematocrit (0.3-4%), hemoglobin (0.3-4%), and mean corpuscular hemoglobin (0.8-2%). In subjects who had quit smoking within two years before blood measurement, hematological characteristics in most cells were similar as in never smokers, whereas normal counts of lymphocytes and monocytes were observed only 2-5 years after quitting., Conclusions: Our findings suggest a marked influence of current smoking habits on leukocyte counts and, to a lesser extent, on counts of erythrocytes and platelets. Following smoking cessation, at least five years have to pass before changes in all hematological parameters may return to normal values.

In several population-based studies in the past urine samples were collected and stored for future research. We set out to determine the reliability of using such samples for genotyping DNA markers in epidemiologic research. A source of DNA extracted from exfoliated nucleated cells in urine is provided by the DOM cohort, in which specimens were collected 15-25 years ago. We have examined the quality of the DNA in 48 of these samples by measuring the amount of DNA isolated and its ability to provide an adequate PCR template for amplicons of different lengths. MTHFR polymorphism was analyzed in 644 specimens to determine the inter- and intraobserver reproducibility. Although the DNA amount was variable, 26 to 89% of the samples, depending both on the length of the PCR amplicon and on PCR conditions, yielded a visible PCR product. The intra- and interobserver agreements were comparable (kappa 0.86 and 0.88, respectively). Our results demonstrate that frozen urine samples can be used for DNA typing studies in women after prolonged periods of storage, but with sometimes unpredictable results. Ultimately, the genotype success rate was 89.3%. Urine collection can be considered as a useful method of obtaining DNA in large cohort studies and other circumstances when blood samples cannot be obtained or have not been stored., ((c) 2002 Elsevier Science (USA))

Objective: We evaluated the effect of meat consumption and cigarette smoking in combination with N-acetyltransferases 1 and 2 (NAT1 and NAT2), and glutathione S-transferase M1 (GSTM1) genotypes on colorectal cancer., Methods: From a Dutch prospective study, after 8.5 years of follow-up, data of 102 incident colorectal cancer cases and a random sample of 537 controls frequency-matched for gender and age were analyzed. Baseline information on dietary and smoking habits, as well as blood samples for DNA isolation and genotyping, were available., Results: Red meat intake increased colorectal cancer risk among men (OR 2.7; 95% CI 1.1-6.7 highest vs. lowest intake), whereas poultry and fish decreased risk among women (OR 0.5; 95% CI 0.2-1.07). Cigarette smoking for at least 16 years increased colorectal cancer risk among former smokers only (OR 2.7; 95% CI 1.0-7.4), compared to those having smoked for 15 years or less. NAT1 and NAT2 polymorphisms did not significantly modify these associations. High consumption of poultry and fish was inversely associated with colorectal cancer only in the presence of GSTM1., Conclusions: In this study meat consumption and former long-term smoking were associated with colorectal cancer. Associations of colorectal cancer with different types of meat were modified by gender and GSTM1 genotype.

Objective: Epidemiologic studies suggest that subjects with elevated plasma concentrations of insulin-like growth factor (IGF)-I are at increased risk of developing cancer. The objective of our study was to assess whether cancer risk factors such as lack of physical activity, obesity, and central body fat distribution are associated with plasma levels of IGF-I and related proteins (i.e. IGF binding proteins 1-3 and C-peptide)., Methods: A cross-sectional study was conducted in a population of 225 premenopausal women, aged 49-57, participating in the Prospect-EPIC study in the Netherlands. Plasma concentrations of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and C-peptide were determined. On the day of blood collection height, weight, and waist and hip circumference were measured. Habitual physical activity was assessed using a validated self-administered questionnaire., Results: Mean concentrations of plasma IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and C-peptide were 156.1, 14.3, 434.4, 3062, and 2.86 ng/ml, respectively. Women in the highest tertile for physical activity had lower plasma concentrations of IGF-I, IGFBP-3, and C-peptide, and higher concentrations of IGFBP-1 and IGFBP-2, as compared to women in the lowest tertile. However, these differences were not statistically significant. BMI and related measures were significantly inversely associated with IGFBP-1 and IGFBP-2, and positively with IGFBP-3 and C-peptide. Linear regression analyses showed that the non-significant association of physical activity with components of the plasma IGF system was further attenuated by adjusting for obesity and central body fat distribution., Conclusions: Our data suggest that an active lifestyle is not independently associated with the plasma IGF system. We did confirm that a lean body shape is associated with higher concentrations of IGFBP-1 and IGFBP-2, and possibly also with lower concentrations of IGF-I and IGFBP-3.

Background: Epidemiologic studies suggest that tea consumption may reduce the risk of cardiovascular diseases, but results are inconsistent. Catechins, which belong to the flavonoid family, are the main components of tea and may be responsible for the alleged protective effect. Taking catechin sources other than tea into account might clarify the reported associations., Objective: The objective was to evaluate the association between catechin intake and the incidence of and mortality from ischemic heart disease and stroke., Design: We evaluated the effect of a high catechin intake by using data from the Zutphen Elderly Study, a prospective cohort study of 806 men aged 65-84 y at baseline in 1985., Results: The mean (+/-SD) catechin intake at baseline was 72 +/- 47.8 mg, mainly from black tea, apples, and chocolate. A total of 90 deaths from ischemic heart disease were documented. Catechin intake was inversely associated with ischemic heart disease mortality; the multivariate-adjusted risk ratio in the highest tertile of intake was 0.49 (95% CI: 0.27, 0.88; P for trend: 0.017). After multivariate adjustment, catechin intake was not associated with the incidence of myocardial infarction (risk ratio in the highest tertile of intake: 0.70; 95% CI: 0.39, 1.26; P for trend: 0.232). After adjustment for tea consumption and flavonol intake, a 7.5-mg increase in catechin intake from sources other than tea was associated with a tendency for a 20% reduction in ischemic heart disease mortality risk (P = 0.114). There was no association between catechin intake and stroke incidence or mortality., Conclusion: Catechins, whether from tea or other sources, may reduce the risk of ischemic heart disease mortality but not of stroke.

Objective: To study the intake of catechins in the Dutch population and to assess the relation between catechin intake and other dietary factors. Catechins, dietary components that belong to the flavonoid family, potentially protect against chronic diseases such as cancer and cardiovascular diseases. Catechins are the major components of tea, but they are present in many other plant foods as well., Design: Data were used from a nationwide dietary survey carried out in 1998 among a representative sample of 6200 Dutch men and women aged 1-97y. Dietary data were collected using a 2 day dietary record method., Results: The average daily catechin intake was 50 mg (s.d. 56 mg/day). Catechin intake increased with age, and the intake was higher in women (60 mg/day) than in men (40 mg/day). Tea was the main catechin source in all age groups, whereas chocolate was second in children, and apples and pears were second in adults and elderly. Catechin intake was lower in smokers than in non-smokers, and increased with socio-economic status. A high intake was associated with a high intake of fiber (r = 0.20), vitamin C (r = 0.17) and beta-carotene (r = 0.10)., Conclusions: Catechins are quantitatively important bioactive components of the daily diet, which should be taken into account when studying the relation between diet and chronic diseases. Catechin intake is only moderately associated with the intake of other nutrients, but much stronger with certain health behaviours such as smoking.

The European Prospective Investigation into Cancer and Nutrition (EPIC), which has been established in order to investigate the relations between nutrition and cancer, was initiated in 1990 and involves 10 European countries with heterogeneous dietary patterns and differing cancer incidence rates. This manuscript presents the design, recruitment and baseline characteristics of the Prospect-EPIC cohort co-ordinated in Utrecht, The Netherlands. The cohort is based on volunteers recruited among women participating in a regional breast cancer screening program. It comprises of 17,357 subjects aged 50-69 years at enrolment from Utrecht and vicinity, who have consented to participate in the study and its follow-up. Each participant filled out a general questionnaire and a food frequency questionnaire. Participants were also physically examined and have donated a blood sample. Participation rate was 34.5%. Blood samples were donated by most participants (97.5%) and detailed informed consents were obtained from 87.4% of participants. Mean age at enrolment was 57 years. Anthropometric, lifestyle and morbidity characteristics of the cohort population did not differ largely from those of similar study populations in The Netherlands. Based on the Prospect-EPIC population, we intend to conduct prospective total cohort, nested case-control or case-cohort studies, in order to investigate relations between consumption of certain food groups or nutrients and chronic diseases, including hormone dependant cancers such as breast, colon, endometrial and ovary cancers.

Plant foods are generally considered to be beneficial for health. A higher consumption of fruits, and to a lesser extent vegetables, is consistently associated with a lower risk of stomach cancer. Results on the association between stomach cancer and grain consumption are less clear. We associated plant food consumption with 25-year stomach cancer mortality at population level in the Seven Countries Study. Around 1960, > 12,000 men aged 40-59 years from 7 countries and 16 cohorts were enrolled. In each cohort, dietary information was collected in small random samples. Crude and adjusted associations were calculated for a change of 10% of mean intake. Results differed for the plant foods studied: an inverse association was observed for fruits (adjusted rate ratio = 0.96, 95% confidence interval = 0.91-0.99), a positive relation for refined grains (adjusted rate ratio = 1.07, 95% confidence interval = 1.03-1.12), and no association for total plant foods, vegetables, whole grains, and potatoes. A high intake of refined grains was correlated with a low consumption of fruits. In conclusion, high intake of refined grains may increase stomach cancer risk. However, because adjustment could only be limited in this study, high intake of refined grains may just reflect the deleterious effect of a diet low in fruits or other characteristics associated with low fruit consumption.

Background: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor., Purpose: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease., Methods: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel., Results: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease., Conclusions: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

The authors studied the intake of vegetables, fruits, beta-carotene, and vitamins C and E in relation to the incidence of lung cancer. For 561 men from the town of Zutphen, the Netherlands, dietary history information was obtained in 1960, 1965, and 1970. During 1971-1990, 54 new cases of lung cancer were identified. The data were analyzed using Cox proportional hazard analyses, adjusting for age, pack-years of cigarettes, and energy intake. No relation between intake of vitamin E and lung cancer risk was seen. For vitamin C intake, the results pointed to an inverse association, although not entirely consistently. Furthermore, it was observed that participants with low stable intakes (i.e., low in 1960, 1965, and 1970) of vegetables, fruits, and beta-carotene experienced more than twofold increased relative risks of lung cancer than those with high stable intakes. For participants with low average intakes, relative risks were much lower and not statistically significant. The authors conclude that there is no apparent relation of vitamin E to lung cancer risk; however, for beta-carotene, vitamin C, vegetables, and fruit, most studies, including the present one, suggest weak inverse associations. The use of repeated intake measurements to select subgroups with stable, highly contrasting intakes may be a promising approach for studying diet-cancer relations.

Background: A self-administered semi-quantitative food frequency questionnaire (FFQ) was developed for the Dutch cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: The reproducibility and relative validity of nutrient intake as assessed by this questionnaire were investigated in a population of 121 men and women. To assess the relative validity, 12 monthly 24-hour recalls served as reference method, together with four determinations of 24-hour urinary nitrogen excretion, predicted basal metabolic rate, and serum beta-carotene and alpha-tocopherol levels., Results: Protein and among women, energy intake were underestimated by the questionnaire compared to urinary nitrogen excretion and the basal metabolic rate, respectively. The underestimation for protein decreased with increasing protein intake. Pearson correlation coefficients between nutrient intakes assessed by repeated questionnaires ranged from 0.70 to 0.94 among men and from 0.59 to 0.94 among women. Correlation coefficients between nutrient intakes assessed by the questionnaire and 24-hour recalls ranged from 0.26 to 0.83 for men and from 0.35 to 0.90 for women, with medians of 0.59 and 0.58, respectively. Correlation coefficients between 0.2 and 0.5 were observed for beta-carotene and vitamin C for men and for beta-carotene and vitamin E for women. Associations with serum beta-carotene (r = -0.16 for men; 0.13 for women) and alpha-tocopherol (0.23 and 0.15, respectively) were much poorer than those obtained with 24-hour recalls. Correlations between protein intake and 24-hour urinary nitrogen excretion were 0.47 and 0.53, respectively., Conclusions: The FFQ seems adequate for ranking subjects according to intake of energy, macronutrients, dietary fibre and retinol, but it does not yield such good results for beta-carotene, vitamin C for men, vitamin E for women.

Background: A physical activity questionnaire was developed with the aim to estimate usual individual daily energy expenditure. The questionnaire focused on the number of hours usually spent on various activities. In a pilot study it was tested for repeatability and validity in a population of 126 Dutch adults (64 men, 62 women)., Methods: For assessment of repeatability the questionnaire was administered three times during the course of 1 year. A four-times-repeated 3-day activity diary was used as a reference instrument to evaluate validity., Results: Differences in mean energy expenditure among repeated administrations of the questionnaire were small and not significant. Spearman's test-retest correlation coefficients for total energy expenditure for men were 0.76 [95% confidence interval (CI) 0.63-0.85] and 0.70 (95% CI 0.54-0.81) at 5 and 11 months, respectively, and for women were 0.58 (95% CI 0.36-0.74) and 0.71 (95% CI 0.54-0.82). There was a significant trend showing increasing mean diary energy expenditure for successive tertiles of questionnaire energy expenditure. The correlation between the questionnaire and the diary was 0.66 (95% CI 0.49-0.78) for men and 0.43 (95% CI 0.18-0.63) for women., Conclusions: It was concluded that this questionnaire is a useful tool for estimating energy expenditure in epidemiological studies.

Background: A self-administered food frequency questionnaire was developed for the Dutch cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Habitual consumption of 178 food items can be calculated from the questionnaire data., Methods: Reproducibility and relative validity for food group intake were investigated in a population of 121 Dutch men and Women. The questionnaire was administered three times at 6-month intervals in order to determine the reproducibility. To assess the relative validity 12 monthly 24-hour recalls served as the reference method., Results: Spearman rank order correlation coefficients between estimates of food group intake assessed by repeated questionnaires ranged from 0.45 to 0.92. For men, Spearman correlation coefficients between estimates of food group intake based on the questionnaire and those based on 24-hour recalls ranged from 0.21 for cooked vegetables to 0.78 for sugar and sweet products, with a range of 0.61. For women the median was 0.53, with a minimum of 0.31 for vegetables and a maximum of 0.87 for alcoholic beverages. The photographs in the questionnaire for the estimation of portion sizes contributed little to the relative validity of the ranking of subjects. However, on the group level most median food group estimates based on photographic portion sizes were closer to the median intakes as assessed by 24-hour recalls than those based on standard portion sizes., Conclusions: The questionnaire seems adequate for ranking Dutch EPIC subjects according to intake of most food groups, although the relative validity for some food groups, such as vegetables and fish, remains of concern.

Background: Gallstones and obesity have been suggested as risk factors for cancer of the biliary tract. Since both factors are related to diet, we studied the relationship between dietary intake and the cancer of interest in a population-based case-control study., Methods: The study population comprised 111 patients and 480 controls. Food intake was assessed by means of a semiquantitative food frequency questionnaire. Estimates of the intake of foods and micronutrients were obtained from cases and controls themselves (direct respondents) or from relatives (indirect respondents). Participants were categorized into tertiles of intake. Risk ratios were estimated by logistic regression analysis., Results: The major findings are a monotonic decrease in risk associated with the consumption of vegetables (ORs 1.0, 0.7, 0.4, P value trend < 0.01) and a monotonic increase in risk associated with sugar added to drinks and desserts (ORs 1.0, 1.3, 2.5; P value trend < 0.01)., Conclusions: The finding on added sugar corresponds to our earlier report that the group monosaccharides and disaccharides is a potential risk factor for this cancer. Sugar may influence bile composition through lipoprotein metabolism. The protective effect of vegetables is in accordance with the reported inverse relationship between vegetables and many epithelial cancers of the alimentary tract.

Background: In a pilot study for the European Prospective Investigation into Cancer and Nutrition (EPIC) a modification of the Baecke questionnaire on physical activity was tested for repeatability and relative validity in a population of 134 men and women aged 20-70 years., Methods: For the assessment of repeatability Pearson's correlation coefficients and percentages of agreement after classification in tertiles were computed between administrations of the questionnaire at baseline, and after 5 and 11 months. Relative validity was determined by comparing the questionnaire to a four times repeated 3-day activity diary., Results: Repeatability after 5 and 11 months was good, with test-retest correlation coefficients between 0.65 and 0.89 for main sections of the questionnaire. The percentages of agreement, exceeding chance (Cohen's kappa) were 57% and 56% for men (at 5 and 11 months respectively) and 41% and 46% for women. The correlations with the diaries were 0.56 in men and 0.44 in women. Agreement apart from chance between classification in tertiles for both methods was 35% for men and 10% for women., Conclusions: These data show that repeatability is good and relative validity as compared to an activity diary is moderate but well within the range of values found in other studies. The questionnaire is more valid in men than in women.

Although cancer of the biliary tract is a highly fatal disease, the relationship with modifiable, life style-related factors is hardly studied. Between 1984 and 1987 we conducted a case-control study of 114 patients and 487 controls from the general population. An interviewer-administered questionnaire was used to collect information on life-time smoking habits and life-time alcohol consumption. The information was obtained either from the subjects themselves (direct response) of from relatives (indirect response). Results show that neither smoking at the time of interview (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.9-2.4) nor smoking 2, 5 or 10 years before were associated significantly with the cancer. Alcohol consumption at the time of interview (OR 1.0; 95% CI 0.6-1.5) or drinking 2, 5 or 10 years before were not significantly associated either. Among current alcohol drinkers, long-term consumers had a reduced risk (duration of use > 38 years vs < 25 years: OR 0.4; 95% CI 0.1-0.9) and late starters an elevated risk (starting age > 38 years vs < 21 years: OR 2.7, 95% CI 1.0-7.5). A modifying effect of alcohol consumption on the smoking-cancer relationship was observed: the risk for current smokers was increased only when they did not drink alcohol at that point in time (OR 3.4, 95% CI 1.3-8.5). Our results indicate that long-term moderate alcohol use might be protective against cancer of the biliary tract, whereas smoking might be a risk factor for this cancer.

Although gallstones and obesity are important risk factors for biliary tract cancer, the relation between diet and this type of cancer has not been studied in detail. Between 1984 and 1988 we conducted a case-control study of 111 cases of biliary tract cancer and 480 controls from the general population. Food intake was assessed by means of a semiquantitative food frequency questionnaire. Estimates of the total energy intake and the intake of macronutrients were obtained from the patients and controls themselves (direct respondents) or from relatives (indirect respondents). The major finding is that the risk associated with the intake of sugars (i.e. the combined intake of monosaccharides and disaccharides), independent of other sources of energy, is more than doubled for indirect respondents and for both respondent groups combined. A biological explanation for the fact that the intake of sugars may be a risk factor for biliary tract cancer might be based on the relationships between sugar, blood lipids and gallstone formation.

As part of the "IARC International Register of Persons Exposed to Phenoxy Herbicides and Contaminants," a cohort of workers who manufacture and prepare chlorophenoxy herbicides was recruited in The Netherlands. The cohort comprised 2,310 workers from two plants, operated by different companies, who were followed during the periods 1955-1985 and 1965-1986, respectively. In 1963, there had been an industrial accident in one factory with concomitant release of dioxin into the environment. Loss to follow-up was 3%. Mortality data on 963 exposed and 1,111 nonexposed men were evaluated by external and internal comparison. Compared with national rates, total mortality (94 deaths, standardized mortality ratio [SMR] = 101; 95% confidence interval [CI], 82-124) and cancer mortality (31 deaths, SMR = 107; 95% CI, 73-152) for exposed workers were not significantly increased. A statistically insignificant increase was observed for non-Hodgkin's lymphoma (2 deaths, SMR = 299; 95% CI, 36-1,078). No cases of soft-tissue sarcoma were encountered. There was no increase in either total mortality (25 deaths, SMR = 111; 95% CI, 72-163) or cancer mortality (10 deaths, SMR = 137; 95% CI, 66-252) among the 139 workers probably exposed to dioxins during the 2,4,5-trichlorophenol production accident or the subsequent clean-up operations. Compared with nonexposed workers, exposed workers did not exhibit a higher total mortality (rate ratio [RR] = 1.28; 95% CI, 0.89-1.82). Mortality due to all cancers (RR = 1.7; 95% CI, 0.9-3.4) and respiratory cancer (RR = 1.7; 95% CI, 0.5-6.3) was insignificantly elevated. These findings suggest that the increases in cancer mortality among workers exposed to phenoxy herbicides and chlorophenols may be attributable to chance. Lack of power prevented evaluation with respect to specific cancers.

From 1984 to 1988 a population-based case-control study was carried out in the Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between the habitual lifetime consumption of alcohol, coffee and tea and exocrine pancreatic carcinoma in 176 cases and 487 controls. An interviewer-administered questionnaire was used to ascertain major life events and obtain estimates of consumption (ever-never) and frequency of consumption throughout life. Logistic regression analyses yielded odds ratios adjusted for age, sex, response status, smoking, dietary intake of energy and vegetables and of alcoholic or non-alcoholic drinks. When compared with data from non-drinkers, the cumulative lifetime consumption of all types of alcohol in grams of ethanol (ORs 1.00, 0.97, 0.93, 1.25, p trend 0.55), beer, spirits, red wine and fortified wine was not related to risk. The consumption of white wine was inversely associated with risk (OR 0.41, 95% CI 0.24-0.70). The uniformly reduced risk estimates for the lifetime number of drinks of white wine were based on small numbers (ORs 1.00, 0.44, 0.25, 0.40, p trend 0.001). When compared with data from non-drinkers, our findings suggest an inverse dose-response relationship for the lifetime consumption of coffee (ORs 1.00, 0.72, 0.37, 0.58, p trend 0.06), whereas lifetime consumption of tea and of ground, instant and decaffeinated coffee was not associated with risk. The absence of an effect of lifetime consumption of decaffeinated coffee may be due to the small numbers of subjects. These results further strengthen existing evidence against a positive association between consumption as well as lifetime consumption of (sources of) alcohol, tea or coffee and the development of exocrine pancreatic cancer.

From 1984 to 1988 a population-based case-control study was carried out in the Netherlands in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between habitual, life-time consumption of varieties of tobacco and exocrine pancreatic carcinoma in 176 cases and 487 controls. An interviewer-administered questionnaire was used to list major life events and obtain estimates of usual frequency of tobacco consumption throughout life. About 58% of patients were interviewed directly. After adjustment for age, gender, response status, energy intake and consumption of vegetables compared with never-smokers, a positive dose-response effect of smoking of life-time number of total cigarettes, i.e. non-filter and filter, emerged (OR 1.00, 1.35, 1.40 and 2.10, p-value trend less than 0.05). Results of simultaneous estimation of the effects of life-time smoking of non-filter and filter cigarettes suggest that the effect was present primarily in non-filter cigarettes. The dose-response relationship was present in current smokers only. Compared with never-smokers, the risk pattern among relatively recent quitters, i.e. 2 to 14 years previously, still suggested a positive effect of past smoking (OR for low smokers 1.99, 95% CI 0.79-4.99 and for high smokers 1.69, 95% CI 0.63-4.58). The risk of quitting 15 years or more could be examined in the low smoking group only and was no different from those who had never smoked (OR 1.02, 95% CI 0.47-2.20). In brief, our results suggest that, independent of usual past intake of energy and vegetables, life-time smoking of cigarettes influences the development of exocrine pancreatic cancer, whereas cessation of smoking of cigarettes for 15 years or more reduces the risk to the levels found among those who have never smoked.

During 1984-88 a population-based case-control study was carried out in The Netherlands in collaboration with the International Agency for Research on Cancer in order to further explore the possible relationship between diet and exocrine pancreatic carcinoma. Past habitual dietary intake was assessed in 164 cases and 480 controls. This is the first series of population-based studies of pancreas cancer to perform a comprehensive assessment of diet. The results of logistic regression analysis, controlled for age, gender and total cigarette consumption, suggested a positive association with past habitual intake of energy in directly interviewed patients (OR highest versus lowest quintile 3.35; 95% confidence interval 1.51-7.18). No indication of an effect of Quetelet index was found. When maximum-weight-ever-achieved was used, nonsignificantly reduced risks were observed for the upper 4 quintiles of "maximum" Quetelet index. After controlling for age, gender, response status and total cigarette consumption, a positive relationship with habitual past intake of total carbohydrates was observed (OR 2.40; 95% confidence interval 1.44-3.99). The effect decreased considerably when the analysis was restricted to subjects who reported stable long-term dietary intake. After controlling for age, gender, total cigarette consumption and response status, a significant, positive association between pancreatic cancer and past habitual intake of simple sugars was found (OR 1.95; 95% confidence interval 1.24-3.07). Among those who reported stable long-term dietary intake, no effect was seen. The positive effect of simple sugars was present in males only (OR 2.15; 95% confidence interval 1.18-3.93) and was smaller in men who reported long-term stable dietary intake. Our findings suggest that the development of exocrine pancreatic carcinoma is positively related to past habitual intake of total energy, total carbohydrates and simple sugars, whereas no relationship with body-mass index was observed.