Christine L. Parr

The impact of dietary and lifestyle risk factors on risk of colorectal cancer: A quantitative overview of the epidemiological evidence

Colorectal cancer is a major cause of cancer mortality and is considered to be largely attributable to inappropriate lifestyle and behavior patterns. The purpose of this review was to undertake a comparison of the strength of the associations between known and putative risk factors for colorectal cancer by conducting 10 independent meta‐analyses of prospective cohort studies. Studies published between 1966 and January 2008 were identified through EMBASE and MEDLINE, using a combined text word and MESH heading search strategy. Studies were eligible if they reported estimates of the relative risk for colorectal cancer with any of the following: alcohol, smoking, diabetes, physical activity, meat, fish, poultry, fruits and vegetables. Studies were excluded if the estimates were not adjusted at least for age. Overall, data from 103 cohort studies were included. The risk of colorectal cancer was significantly associated with alcohol: individuals consuming the most alcohol had 60% greater risk of colorectal cancer compared with non‐ or light drinkers (relative risk 1.56, 95% CI 1.42–1.70). Smoking, diabetes, obesity and high meat intakes were each associated with a significant 20% increased risk of colorectal cancer (compared with individuals in the lowest categories for each) with little evidence of between‐study heterogeneity or publication bias. Physical activity was protective against colorectal cancer. Public‐health strategies that promote modest alcohol consumption, smoking cessation, weight loss, increased physical activity and moderate consumption of red and processed meat are likely to have significant benefits at the population level for reducing the incidence of colorectal cancer.

Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study

BACKGROUND In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424 519 participants

BACKGROUND Excess bodyweight is an established risk factor for several types of cancer, but there are sparse data from Asian populations, where the proportion of overweight and obese individuals is increasing rapidly and adiposity can be substantially greater for the same body-mass index (BMI) compared with people from Western populations. METHODS We examined associations of adult BMI with cancer mortality (overall and for 20 cancer sites) in geographic populations from Asia and from Australia and New Zealand (ANZ), within the Asia-Pacific Cohort Studies Collaboration, by use of Cox regression analysis. Pooled data from 39 cohorts (recruitment 1961-99, median follow-up 4 years) were analysed for 424,519 participants (77% Asian; 41% female; mean recruitment age 48 years) with individual data on BMI. FINDINGS After excluding those with follow-up of less than 3 years, 4872 cancer deaths occurred in 401,215 participants. Hazard ratios for cancer sites with increased mortality risk in obese (BMI > or = 30 kg/m(2)) compared with normal weight participants (BMI 18.5-24.9 kg/m(2)) were: 1.21 (95% CI 1.09-1.36) for all-cause cancer (excluding lung and upper aerodigestive tract), 1.50 (1.13-1.99) for colon, 1.68 (1.06-2.67) for rectum, 1.63 (1.13-2.35) for breast in women 60 years or older, 2.62 (1.57-4.37) for ovary, 4.21 (1.89-9.39) for cervix, 1.45 (0.97-2.19) for prostate, and 1.66 (1.03-2.68) for leukaemia (all after left censoring at 3 years). The increased risk associated with a 5-unit increase in BMI for those with BMI of 18.5 kg/m(2) or higher was 1.09 (95% CI 1.04-1.14) for all cancers (excluding lung and upper aerodigestive tract). There was little evidence of regional differences in relative risk of cancer with higher BMI, apart from cancers of the oropharynx and larynx, where the association was inverse in ANZ and absent in Asia. INTERPRETATION Overweight and obese individuals in populations across the Asia-Pacific region have a significantly increased risk of mortality from cancer. Strategies to prevent individuals from becoming overweight and obese in Asia are needed to reduce the burden of cancer that is expected if the obesity epidemic continues. FUNDING National Health and Medical Research Council of Australia, Health Research Council of New Zealand, and Pfizer Inc.

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.

Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up.

In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow‐up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow‐up. Information on diet and lifestyle was collected at baseline. A calibration study in a subsample was used to correct for dietary measurement errors. When comparing the highest vs. lowest quintile of intake, we found an inverse association between total intake of V&F and GC risk [hazard ratio (HR) 0.77; 95% confidence interval (CI) 0.57–1.04; p for trend 0.02], between fresh fruit and risk of the diffuse type (HR 0.59; 95% CI 0.36–0.97; p for trend 0.03) and an inverse association between citrus fruit and risk of cardia cancer (HR 0.61; 95% CI 0.38–1.00, p for trend 0.01). Although calibration revealed somewhat stronger inverse associations, none of the risks reached statistical significance. There was no association between total or specific vegetables intake and GC risk. The inverse association between fresh fruit and citrus fruits and risk of GC seems to be restricted to smokers and the Northern European countries. Fresh fruit and citrus fruit consumption may protect against diffuse and cardia GC, respectively.

Test-retest reproducibility of a food frequency questionnaire (FFQ) and estimated effects on disease risk in the Norwegian Women and Cancer Study (NOWAC)

BackgroundThe Norwegian Women and Cancer Study (NOWAC) is a national population-based cohort study with 102 443 women enrolled at age 30–70 y from 1991 to 1997. The present study was a methodological sub-study to assess the test-retest reproducibility of the NOWAC food frequency questionnaire (FFQ), and to study how measurement errors in the data can affect estimates of disease risk.MethodsA random sample of 2000 women aged 46–75 y was drawn from the cohort in 2002. A self-instructive health and lifestyle questionnaire with a FFQ section was mailed to the same subjects twice (test-retest), about three months apart, with a response rate of 75%. The FFQ was designed to assess habitual diet over the past year. We assess the reproducibility of single questions, food groups, energy, and nutrients with several statistical measures. We also demonstrate the method of regression calibration to correct disease risk estimates for measurement error. Alcohol intake (g/day) and high blood pressure (yes/no) is used in the example.ResultsFor single foods there were some indications of seasonal reporting bias. For food groups and nutrients the reliability coefficients ranged from 0.5–0.8, and Pearsons r, Spearmans rs, and two intraclass correlation coefficients gave similar results. Although alcohol intake had relatively high reproducibility (r = 0.72), odds ratio estimates for the association with blood pressure were attenuated towards the null value compared to estimates corrected by regression calibration.ConclusionThe level of reproducibility observed for the FFQ used in the NOWAC study is within the range reported for similar instruments, but may attenuate estimates of disease risk.

Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition

Objective:To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Between 1995 and 2000, 36 034 subjects, aged between 35–74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall.Results:Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol.Conclusions:Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease.

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.

Recall Bias in Melanoma Risk Factors and Measurement Error Effects: A Nested Case-Control Study Within the Norwegian Women and Cancer Study

Case-control studies of melanoma have the potential for recall bias after much public information about the relation with ultraviolet radiation. Recall bias has been investigated in few studies and only for some risk factors. A nested case-control study of recall bias was conducted in 2004 within the Norwegian Women and Cancer Study: 208 melanoma cases and 2,080 matched controls were invited. Data were analyzed for 162 cases (response, 78%) and 1,242 controls (response, 77%). Questionnaire responses to several host factors and ultraviolet exposures collected at enrollment in 1991-1997 and in 2004 were compared stratified on case-control status. Shifts in responses were observed among both cases and controls, but a shift in cases was observed only for skin color after chronic sun exposure, and a larger shift in cases was observed for nevi. Weighted kappa was lower for cases than for controls for most age intervals of sunburn, sunbathing vacations, and solarium use. Differences in odds ratio estimates of melanoma based on prospective and retrospective measurements indicate measurement error that is difficult to characterize. The authors conclude that indications of recall bias were found in this sample of Norwegian women, but that the results were inconsistent for the different exposures.