H. B. Bueno-de-Mesquita

General and Abdominal Adiposity and Risk of Death in Europe

BACKGROUND Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

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.

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study

OBJECTIVE To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries

OBJECTIVE To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis. SETTING Twenty-seven centres in 10 European countries participating in the EPIC project. SUBJECTS In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, randomly selected from each EPIC cohort. RESULTS The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits. CONCLUSIONS Total vegetable and fruit intake follows a south-north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.

Evaluation of under- and overreporting of energy intake in the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)

OBJECTIVE To evaluate under- and overreporting and their determinants in the EPIC 24-hour diet recall (24-HDR) measurements collected in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Cross-sectional analysis. 24-HDR measurements were obtained by means of a standardised computerised interview program (EPIC-SOFT). The ratio of reported energy intake (EI) to estimated basal metabolic rate (BMR) was used to ascertain the magnitude, impact and determinants of misreporting. Goldbergs cut-off points were used to identify participants with physiologically extreme low or high energy intake. At the aggregate level the value of 1.55 for physical activity level (PAL) was chosen as reference. At the individual level we used multivariate statistical techniques to identify factors that could explain EI/BMR variability. Analyses were performed by adjusting for weight, height, age at recall, special diet, smoking status, day of recall (weekday vs. weekend day) and physical activity. SETTING Twenty-seven redefined centres in the 10 countries participating in the EPIC project. SUBJECTS In total, 35 955 men and women, aged 35-74 years, participating in the nested EPIC calibration sub-studies. RESULTS While overreporting has only a minor impact, the percentage of subjects identified as extreme underreporters was 13.8% and 10.3% in women and men, respectively. Mean EI/BMR values in men and women were 1.44 and 1.36 including all subjects, and 1.50 and 1.44 after exclusion of misreporters. After exclusion of misreporters, adjusted EI/BMR means were consistently less than 10% different from the expected value of 1.55 for PAL (except for women in Greece and in the UK), with overall differences equal to 4.0% and 7.4% for men and women, respectively. We modelled the probability of being an underreporter in association with several individual characteristics. After adjustment for age, height, special diet, smoking status, day of recall and physical activity at work, logistic regression analyses resulted in an odds ratio (OR) of being an underreporter for the highest vs. the lowest quartile of body mass index (BMI) of 3.52 (95% confidence interval (CI) 2.91-4.26) in men and 4.80 (95% CI 4.11-5.61) in women, indicating that overweight subjects are significantly more likely to underestimate energy intake than subjects in the bottom BMI category. Older people were less likely to underestimate energy intake: ORs were 0.58 (95% CI 0.45-0.77) and 0.74 (95% CI 0.63-0.88) for age (> or =65 years vs. <50 years). Special diet and day of the week showed strong effects. CONCLUSION EI tends to be underestimated in the vast majority of the EPIC centres, although to varying degrees; at the aggregate level most centres were below the expected reference value of 1.55. Underreporting seems to be more prevalent among women than men in the EPIC calibration sample. The hypothesis that BMI (or weight) and age are causally related to underreporting seems to be confirmed in the present work. This introduces further complexity in the within-group (centre or country) and between-group calibration of dietary questionnaire measurements to deattenuate the diet-disease relationship.

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objective:The aim in this study was to assess the association between individual plasma carotenoid levels (α-carotene, β-carotene, lycopene, β-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods.Design:A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included.Results:β-Cryptoxanthin was most strongly correlated with total fruits (FQ r=0.52, 24HDR r=0.39), lycopene with tomato and tomato products (FQ r=0.38, 24HDR r=0.25), and α-carotene with intake of root vegetables (r=0.39) and of total carrots (r=0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R partial 2=17.2%) for β-cryptoxanthin, total carrots (R partial 2=13.4%) and root vegetables (R partial 2=13.3%) for α-carotene, and tomato products (R partial 2=13.8%) for lycopene. For 24HDR, the highest R partial 2 was for fruits in relation to β-cryptoxanthin (7.9%).Conclusions:Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of β-cryptoxanthin, α-carotene, and lycopene in plasma.

Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies

We examined the effect of exposure to chemicals present in the production and spraying of phenoxy herbicides or chloro-phenols in two nested case-control studies of soft tissue sarcoma and non-Hodgkins lymphoma. Eleven sarcoma and 32 lymphoma cases occurring within an international cohort were matched for age, sex, and country of residence with 55 and 158 controls, respectively. Exposures to 21 chemicals or mixtures were estimated by three industrial hygienists who were blind to the subjects case-control status. Excess risk of soft tissue sarcoma was associated with exposure to any phenoxy herbicide [odds ratio (OR) = 10.3; 95% confidence interval (Cl) = 1.2–91] and to each of the three major classes of phenoxy herbicides (2,4-dichlorophenoxyacetic acid, 2,4,5-trichloro-phenoxyacetic acid, and 4-chloro-2-methylphenoxyacetic acid), to any polychlorinated dibenzodioxin or furan (OR = 5.6; 95% CI = 1.1–28), and to 2,3,7,8-tetrachlorodibenzo-p-dioxm (OR = 5.2; 95% CI = 0.85–32). Sarcoma risk was not associated with exposure to raw materials or other process chemicals. In the non-Hodgkins lymphoma study, associations were generally weaker than those found in the study on sarcoma. These findings indicate that workers exposed to phenoxy herbicides and their contaminants are at a higher risk of soft tissue sarcoma.

Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition

We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07–1.41, Ptrend=0.02). After calibration to allow for measurement error, we estimated that a 35-g day−1 increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1–72%, Ptrend=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.

Physical activity of subjects aged 50-64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC)

OBJECTIVE To describe physical activity of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN A cross-sectional analysis of baseline data of a European prospective cohort study. SUBJECTS This analysis was restricted to participants in the age group 50-64 years, which was represented in all EPIC centres. It involved 236 386 participants from 25 centres in nine countries. In each EPIC centre, physical activity was assessed by standardised and validated questions. Frequency distribution of type of professional activity and participation in non-professional activities, and age-adjusted means, medians and percentiles of time dedicated to non-professional activities are presented for men and women from each centre. RESULTS Professional activity was most frequently classified as sedentary or standing in all centres. There was a wide variation regarding participation in different types of non-professional activities and time dedicated to these activities across EPIC centres. Over 80% of all EPIC participants engaged in walking, while less than 50% of the subjects participated in sport. Total time dedicated to recreational activities was highest among the Dutch participants and lowest among men from Malmö (Sweden) and women from Naples (Italy). In all centres, total time dedicated to recreational activity in the summer was higher than in the winter. Women from southern Europe spent the most time on housekeeping. CONCLUSIONS There is a considerable variation of physical activity across EPIC centres. This variation was especially evident for recreational activities in both men and women.

Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC).

We examined the association between self‐reported consumption of fruits and vegetables and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow‐up for cancer incidence were available for 130,544 men in 7 countries recruited into EPIC between 1993 and 1999. After an average of 4.8 years of follow‐up, there were 1,104 incident cases of prostate cancer. The associations of consumption of total fruits, total vegetables, cruciferous vegetables and combined total fruits and vegetables with prostate cancer risk were examined using Cox regression, stratified for recruitment center and adjusted for height, weight and energy intake. There was a wide range in consumption of fruits and vegetables: mean intakes (g/day) in the bottom and top fifths of the distribution, as estimated from 24‐hr recalls in a subsample of participants, were 53.2 and 410.7 for fruits, 97.1 and 242.1 for vegetables and 169.0 and 633.7 for fruits and vegetables combined. No significant associations between fruit and vegetable consumption and prostate cancer risk were observed. Relative risks (95% confidence intervals) in the top fifth of the distribution of consumption, compared to the bottom fifth, were 1.06 (0.84–1.34) for total fruits, 1.00 (0.81–1.22) for total vegetables and 1.00 (0.79–1.26) for total fruits and vegetables combined; intake of cruciferous vegetables was not associated with risk. These results suggest that total consumption of fruits and vegetables is not associated with the risk for prostate cancer.