Heiner Boeing

European prospective investigation into cancer and nutrition (EPIC): study populations and data collection

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35-70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrollment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case-control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.

Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

It is considered that fruit and vegetable (F&V) protect against oesophagus and gastric cancer (GC). However, 2 recent meta‐analyses suggest that the strength of association on GC seems to be weaker for vegetables than for fruit and weaker in cohort than in case‐control studies. No evidence exists from cohort studies about adenocarcinoma of oesophagus (ACO). In 521,457 men and women participating in the EPIC cohort in 10 European countries, information of diet and lifestyle was collected at baseline. After an average of 6.5 years of follow‐up, a total of 330 GC and 65 ACO, confirmed and classified by a panel of pathologists, was used for the analysis. We examined the relation between F&V intake and GC and ACO. A calibration study in a sub‐sample was used to control diet measurement errors. In a sub‐sample of cases and a random sample of controls, antibodies against Helicobacter pylori (Hp) were measured and interactions with F&V were examined in a nested case‐control study. We observed no association with total vegetable intake or specific groups of vegetables and GC risk, except for the intestinal type, where a negative association is possible regarding total vegetable (calibrated HR 0.66; 95% CI 0.35–1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38–1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47–1.22 per 100 g increase) while no association was observed with the non‐cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% CI 0.32–1.64 and 0.77; 95% CI 0.46–1.28 per 100 and 50 g increase, respectively). It seems that Hp infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO.

Overweight, obesity and fat distribution in 50-to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)

OBJECTIVEnTo describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC).nnnDESIGNnA cross-sectional analysis of baseline data of a European prospective cohort study.nnnSUBJECTSnThis analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a health-conscious group. The analysis was restricted to 83 178 men and 163 851 women aged 50-64 years, this group being represented in all centres.nnnMETHODSnAnthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the health-conscious group (UK), anthropometric measures were predicted from self-reports.nnnRESULTSnExcept in the health-conscious group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m-2. The prevalence of obesity (BMI> or =30 kg m(-2)) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (>25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (<10%) in the French centres and the health-conscious group (UK). The prevalence of a large waist circumference or a high waist-to-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands).nnnCONCLUSIONSnAnthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.

Body Size and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition

Background: Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer. Methods: We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity. Results: During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (Pinteraction for waist with BMI, 0.25, 0.02, and 0.05, respectively; Pinteraction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively). Conclusions: These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3252–61)

Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study

Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992–1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR)xa0=xa00.91; 95% confidence interval (95% CI) 0.83–1.00 per 80xa0g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92–1.02) and RRxa0=xa00.89 (95% CI: 0.78–1.02) per 40xa0g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (<120xa0g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.

Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition

Background: Increasing evidence suggests that general obesity [measured by body mass index (BMI)] is positively associated with risk of esophageal adenocarcinoma (EAC). In contrast, previous studies have shown inverse relations with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether body fat distribution, particularly abdominal obesity, is associated with each type of esophageal cancer. Methods: We applied multivariable adjusted Cox proportional hazards regression to investigate the association between anthropometric measures and risk of EAC and ESCC among 346,554 men and women participating in the European Prospective Investigation into Cancer and Nutrition. All statistical tests were two sided. Results: During 8.9 years of follow-up, we documented 88 incident cases of EAC and 110 cases of ESCC. BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with EAC risk [highest versus lowest quintile; relative risk (RR), 2.60; 95% confidence interval (95% CI), 1.23-5.51; Ptrend < 0.01; RR, 3.07; 95% CI, 1.35-6.98; Ptrend < 0.003; and RR, 2.12; 95% CI, 0.98-4.57; Ptrend < 0.004]. In contrast, BMI and waist circumference were inversely related to ESCC risk, whereas WHR showed no association with ESCC. In stratified analyses, BMI and waist circumference were significantly inversely related to ESCC only among smokers but not among nonsmokers. However, when controlled for BMI, we found positive associations for waist circumference and WHR with ESCC, and these associations were observed among smokers and nonsmokers. Conclusion: General and abdominal obesity were associated with higher EAC risk. Further, our study suggests that particularly an abdominal body fat distribution might also be a risk factor for ESCC. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2079–89)

Pathology findings and validation of gastric and esophageal cancer cases in a European cohort (EPIC/EUR-GAST)

Objective. Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). Material and methods. In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. Results. The whole series encompassed 467 cancer cases (gastric and esophageal cancers). Material was available for histopathological validation in 263 cases (56%); in the remaining cases, information was retrieved from the original reports (n=110; 24%) or codes provided by the EPIC centers (n=94; 20%). Among cases submitted to histopathological validation reported originally as unknown histotype or unknown site, a specific diagnosis was made in 95% and 74% of the cases, respectively. In cases for which only the original reports were available, the respective percentages were 46% and 67%. Gastric adenocarcinomas were classified according to site (cardia (29.4%), non-cardia (48.2%) and unknown (22.4%)) and histological type (intestinal (33.4%), diffuse (33.7%) and mixed, unclassified or unknown (32.9%)). Frequency of cardia was higher in Northern countries (35%) than in Mediterranean countries (18%). Conclusions. In addition to providing epidemiological data within the EPIC cohort on gastric and esophageal adenocarcinomas, the results reported here confirm the relevance of a validation study, notably for multicenter studies.

General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non‐cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow‐up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty‐four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HRu2009=u20091.19; 95% CI, 0.63–2.22 and HRu2009=u20093.76; 1.72–8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HRu2009=u20090.35; 0.18–0.68, and HR=4.10; 1.94‐8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HRu2009=u20091.91; 1.09–3.37, and HRu2009=u20092.23; 1.28–3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

Lifetime and baseline alcohol intake and risk of cancer of the upper aero‐digestive tract in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Recent alcohol consumption is an established risk factor for squamous cell carcinoma (SCC) of the upper aero‐digestive tract. In contrast, the role of lifetime exposure to alcohol with regard to risk of SCC is not well established. Historical data on alcohol use are available in 271,253 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 2,330,381 person years, 392 incident SCC cases (279 men and 113 women) were identified. Cox regression was applied to model sex‐specific associations between lifetime alcohol intake and SCC risk adjusting for potential confounders including smoking. Compared to men who drank 0.1–6.0 g/day alcohol at lifetime, the relative risks (RR) for developing SCC were significantly increased for men who drank 30.1–60.0 g/day (RR 1.65, 95% confidence interval:1.00–2.71), 60.1–96.0 g/day (RR 2.20, 95%CI 1.23–3.95), and >96.0 g/day, (RR 4.63, 95% CI 2.52–8.48), and for former drinkers (RR 4.14, 95%CI 2.38–7.19). These risk estimates did not considerably change when baseline alcohol intake was analyzed. Compared to women who drank 0.1–6.0 g/day alcohol intake at lifetime, the RR were significantly increased for women who drank >30 g/d (RR 6.05, 95%CI 2.98–12.3). Applying similar categories, the relative risk for baseline alcohol intake was 3.26 (95%CI 1.82–5.87). We observed a stronger association between alcohol intake at lifetime and risk of SCC in women compared to men (p for interaction = 0.045). The strong dose‐response relation for lifetime alcohol use underscores that alcohol is an important risk factor of SCC of the upper aero‐digestive tract throughout life.

Validation of Anthropometric Indices of Adiposity against Whole-Body Magnetic Resonance Imaging – A Study within the German European Prospective Investigation into Cancer and Nutrition (EPIC) Cohorts

Background In epidemiological studies, measures of body fat generally are obtained through anthropometric indices such as the body mass index (BMI), waist (WC), and hip circumferences (HC). Such indices, however, can only provide estimates of a person’s true body fat content, overall or by adipose compartment, and may have limited accuracy, especially for the visceral adipose compartment (VAT). Objective To determine the extent to which different body adipose tissue compartments are adequately predicted by anthropometry, and to identify anthropometric measures alone, or in combination to predict overall adiposity and specific adipose tissue compartments, independently of age and body size (height). Methods In a sub-study of 1,192 participants of the German EPIC (European Prospective Investigation into Cancer and Nutrition) cohorts, whole-body MRI was performed to determine adipose and muscle tissue compartments. Additional anthropometric measurements of BMI, WC and HC were taken. Results After adjusting for age and height, BMI, WC and HC were better predictors of total body volume (TBV), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) than for VAT, coronary adipose tissue (CAT) and skeletal muscle tissue (SMT). In both sexes, BMI was the best predictor for TBV (men: ru200a=u200a0.72 [0.68–0.76], women: ru200a=u200a0.80 [0.77–0.83]) and SMT (men: ru200a=u200a0.52 [0.45–0.57], women: ru200a=u200a0.48 [0.41–0.54]). WC was the best predictor variable for TAT (ru200a=u200a0.48 [0.41–0.54]), VAT (ru200a=u200a0.44 [0.37–0.50]) and CAT (ru200a=u200a0.34 [0.26–0.41]) (men), and for VAT (ru200a=u200a0.42 [0.35–0.49]) and CAT (ru200a=u200a0.29 [0.22–0.37]) (women). BMI was the best predictor for TAT (ru200a=u200a0.49 [0.43–0.55]) (women). HC was the best predictor for SAT (men (ru200a=u200a0.39 [0.32–0.45]) and women (ru200a=u200a0.52 [0.46–0.58])). Conclusions Especially the volumes of internal body fat compartments are poorly predicted by anthropometry. A possible implication may be that associations of chronic disease risks with the sizes of internal body fat as measured by BMI, WC and HC may be strongly underestimated.