Heinz Freisling

Region-Specific Nutrient Intake Patterns Exhibit a Geographical Gradient within and between European Countries

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study

BACKGROUND In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. DESIGN The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. RESULTS After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. CONCLUSION Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.

Obesity and cancer: An update of the global impact

In view of the growing global obesity epidemic, this paper reviews the relation between recent trends in body mass index (BMI) and the changing profile of cancer worldwide. By examining seven selected countries, each representing a world region, a pattern of increasing BMI with region and gender-specific diversity is noted: increasing levels of BMI were most pronounced in the Middle East (Saudi Arabia), rather modest in Eastern Asia (India) and generally more rapid in females than in males. This observation translates into a disproportionate distribution of cancer attributable to high levels of BMI, ranging by sex from 4-9% in Saudi Arabia and from 0.2-1.2% in India. Overweight and obesity may also influence cancer outcomes, and hence have a varying impact on cancer survival and death in different world regions. Future challenges in cancer studies exploring the association with overweight and obesity concern the measurement of adiposity and its potentially cumulative effect over the life course. Given the limitations of BMI as an imperfect measure of body fatness, routine anthropometric data collection needs to be extended to develop more informative measures, such as waist circumference in settings where the gold standard tools remain unaffordable. Furthermore, questions surrounding the dose-response and timing of obesity and their associations with cancer remain to be answered. Improved surveillance of health risk factors including obesity as well as the scale and profile of cancer in every country of the world is urgently needed. This will enable the design of cost-effective actions to curb the growing burden of cancer related to excess body weight.

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case–control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X‐ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non‐significant lower CRC risk (IRR = 0.92, 95% CI: 0.82–1.03 per 25 μg/L increase). However, sub‐group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70–0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82–0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72–0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86–1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

Fruit and vegetable consumption and prospective weight change in participants of the European Prospective Investigation into Cancer and Nutrition–Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home, and Obesity study

BACKGROUND Fruit and vegetable consumption might prevent weight gain through their low energy density and high dietary fiber content. OBJECTIVE We assessed the association between the baseline consumption of fruit and vegetables and weight change in participants from 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition study. DESIGN Diet was assessed at baseline in 373,803 participants by using country-specific validated questionnaires. Weight was measured at baseline and self-reported at follow-up in most centers. Associations between baseline fruit and vegetable intakes (per 100 g/d) and weight change (g/y) after a mean follow-up of 5 y were assessed by using linear mixed-models, with age, sex, total energy intake, and other potential confounders controlled for. RESULTS After exclusion of subjects with chronic diseases at baseline and subjects who were likely to misreport energy intakes, baseline fruit and vegetable intakes were not associated with weight change overall. However, baseline fruit and vegetable intakes were inversely associated with weight change in men and women who quit smoking during follow-up. We observed weak positive associations between vegetable intake and weight change in women who were overweight, were former smokers, or had high prudent dietary pattern scores and weak inverse associations between fruit intake and weight change in women who were >50 y of age, were of normal weight, were never smokers, or had low prudent dietary pattern scores. CONCLUSIONS In this large study, higher baseline fruit and vegetable intakes, while maintaining total energy intakes constant, did not substantially influence midterm weight change overall but could help to reduce risk of weight gain in persons who stop smoking. The interactions observed in women deserve additional attention.

The standardized computerized 24-h dietary recall method EPIC-Soft adapted for pan-European dietary monitoring

Background/Objectives:The EPIC-Soft program (the software initially developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) was recommended as the best way to standardize 24-HDRs for future pan-European dietary monitoring. Within European Food Consumption Validation (EFCOVAL), EPIC-Soft was adapted and further developed on various aspects that were required to optimize its use. In this paper, we present the structure and main interview steps of the EPIC-Soft program, after implementation of a series of new specifications deemed to satisfy specific requirements of pan-European monitoring surveys and other international studies.Subjects/Methods:Updates to optimize the EPIC-Soft program were ascertained according to the following stepwise approach: (1) identification of requested specifications to be potentially implemented through an ad hoc ‘EPIC-Soft specifications questionnaire’ sent to past, current and possible future users of the software; (2) evaluation of the specifications in collaboration with two ad hoc task force groups and through a workshop; (3) development of a technical solution for each retained specification; (4) implementation of the specifications by software developers; (5) testing and amendment of bugs.Results:A number of new specifications and facilities were implemented to EPIC-Soft program. In addition, the software underwent a full reprogramming and migration to a modern Windows environment, including changes in its internal architecture and user interface. Although the overall concept and structure of the initial software were not changed substantially, these improvements ease the current and future use of EPIC-Soft and increase further its adaptation to other countries and study contexts.Conclusions:EPIC-Soft is enriched with further functions and facilities expected to fulfil specific needs of pan-European dietary monitoring and risk assessment purposes. The validity, feasibility and relevance of this software for different national and international study designs, and the logistical aspects related to its implementation are reported elsewhere.

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 HR = 1.19; 95% CI, 0.63–2.22 and HR = 3.76; 1.72–8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 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 HR = 1.91; 1.09–3.37, and HR = 2.23; 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.

Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer

Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.

The European Food Consumption Validation Project: conclusions and recommendations

Background/Objectives:To outline and discuss the main results and conclusions of the European Food Consumption Validation (EFCOVAL) Project.Subjects/Methods:The EFCOVAL Project was carried out within the EU Sixth Framework Program by researchers in 11 EU countries. The activities focused on (1) the further development of the EPIC-Soft software (the software developed to conduct 24-h dietary recalls (24-HDRs) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study) and the validation of the 2-day non-consecutive 24-HDR method using EPIC-Soft, (2) defining and investigating the applicability of the most appropriate dietary assessment method to younger age groups and expanding the applicability of the software for use in exposure assessment of some potentially hazardous chemicals and (3) to improve the methodology and statistical methods that estimate usual intake distributions from short-term dietary intake information and develop a methodology to quantify uncertainty in usual intake distributions.Results:The preexisting EPIC-Soft application was reprogrammed into a Windows environment and more than 60 new specifications were implemented in the software. A validation study showed that two non-consecutive EPIC-Soft 24-HDRs are suitable to estimate the usual intake distributions of protein and potassium of European adult populations. The 2-day non-consecutive 24-HDRs in combination with a food propensity questionnaire also appeared to be appropriate to rank individuals according to their fish and fruit and vegetable intake in a comparable way in five European centers. Dietary intake of (young) children can be assessed by the combination of EPIC-Soft 24-HDRs and food recording booklets. The EPIC-Soft-standardized method of describing foods is useful to estimate dietary exposure to potentially hazardous chemicals such as specific flavoring substances. With the developed Multiple Source Method, repeated non-consecutive 24-HDR data in combination with food propensity data can be used to estimate the population distribution of the usual intake by estimating the individual usual intakes.Conclusions:The findings provide sufficient evidence to conclude that the repeated 24-HDR using EPIC-Soft for standardization in combination with a food propensity questionnaire and modeling of usual intake is a suitable method for pan-European surveillance of nutritional adequacy and food safety among healthy adults and maybe in children aged 7 years and older. To facilitate this methodology in other European countries, the next step is to provide and standardize an implementation plan that accounts for maintenance and updates, sampling designs, national surveillance programs, tailored capacity building and training, and linkage to food composition and occurrence databases.

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0–4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow‐up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66–0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67–0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40–0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported.