Search

Background: A high consumption of fruit and vegetables is possibly associated with a decreased risk of colorectal cancer (CRC). However, the findings to date are inconsistent. Objective: We examined the relation between self-reported usual consumption of fruit and vegetables and the incidence of CRC. Design: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 452,755 subjects (131,985 men and 320,770 women) completed a dietary questionnaire in 1992-2000 and were followed up for cancer incidence and mortality until 2006. A multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HRs) and 95% CIs. Results: After an average follow-up of 8.8 y, 2,819 incident CRC cases were reported. Consumption of fruit and vegetables was inversely associated with CRC in a comparison of the highest with the lowest EPIC-wide quintile of consumption (HR: 0.86; 95% CI: 0.75, 1.00; P for trend = 0.04), particularly with colon cancer risk (HR: 0.76; 95% CI: 0.63, 0.91; P for trend < 0.0l). Only after exclusion of the first 2 y of follow-up were these findings corroborated by calibrated continuous analyses for a 100-g increase in consumption: HRs of 0.95 (95% CI: 0.91, 1.00; P = 0.04) and 0.94 (95% CI: 0.89, 0.99; P = 0.02), respectively. The association between fruit and vegetable consumption and CRC risk was inverse in never and former smokers, but positive in current smokers. This modifying effect was found for fruit and vegetables combined and for vegetables alone (P for interaction < 0.01 for both). Conclusions: These findings suggest that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer. This effect may depend on smoking status.

Background: Epidemiologic data suggest that persons with diets rich in fruit and vegetables are at a lower risk of several chronic diseases and mortality than are persons with diets poor in fruit and vegetables. Often, this effect is attributed to antioxidant micronutrients found in plant foods. Objective: We aimed to assess the relation of mortality to the consumption of fruit, vegetables, and other plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids. Design: The study was a prospective study in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up, 562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards regression analysis was used to assess the relation between dietary factors and total mortality. Results: After adjustment for age, sex, and several potential confounders, the hazard ratio for the highest versus the lowest quartile of consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit, 0.72 (0.56, 0.91 ; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98; P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the 'fruit' part of the plant, the seeds). The corresponding figures for antioxidant nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53, 0.87, P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51,0.84; P for trend 0.001) for lycopene. The effect of vitamin C and provitamin A disappeared after adjustment for total antioxidant capacity in plant foods. Conclusions: A high intake of fresh fruit, root vegetables, and fruiting vegetables is associated with reduced mortality, probably as a result of their high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant capacity could partly explain the effect of ascorbic acid and provitamin A but not the association with lycopene. Am J Clin Nutr 2007:85:1634-42. KEY WORDS Mortality, fruit, vegetables, antioxidants, cohort studies

Background: Body weight and body mass index (BMI) are positively related to risk of colon cancer in men, whereas weak or no associations exist in women. This discrepancy may be related to differences in fat distribution between sexes or to the use of hormone replacement therapy (HRT) in women. Methods: We used multivariable adjusted Cox proportional hazards models to examine the association between anthropometric measures and risks of colon and rectal cancer among 368 277 men and women who were free of cancer at baseline from nine countries of the European Prospective Investigation Into Cancer and Nutrition. All statistical tests were two-sided. Results: During 6.1 years of follow-up, we identified 984 and 586 patients with colon and rectal cancer, respectively. Body weight and BMI were statistically significantly associated with colon cancer risk in men (highest versus lowest quintile of BMI, relative risk [RR] = 1.55, 95% confidence interval [CI] = 1.12 to 2.15; [P.sub.trend] = .006) but not in women. In contrast, comparisons of the highest to the lowest quintile showed that several anthropometric measures, including waist circumference (men, RR = 1.39, 95% CI = 1.01 to 1.93; [P.sub.trend] = .001; women, RR = 1.48, 95% CI = 1.08 to 2.03; [P.sub.trend] = .008), waist-to-hip ratio (WHR; men, RR = 1.51, 95% CI = 1.06 to 2.15; [P.sub.trend] = .006; women, RR = 1.52, 95% CI = 1.12 to 2.05; [P.sub.trend] = .002), and height (men, RR = 1.40, 95% CI = 0.99 to 1.98; [P.sub.trend] = .04; women, RR = 1.79, 95% CI = 1.30 to 2.46; [P.sub.trend]

Background: Dietary factors are thought to have an important role in gastric and esophageal carcinogenesis, but evidence from cohort studies for such a role is lacking. We examined the risks of gastric cancer and esophageal adenocarcinoma associated with meat consumption within the European Prospective investigation Into Cancer and Nutrition (EPIC) cohort. Methods: A total of 521 457 men and women aged 35-70 years in 10 European countries participated in the EPIC cohort. Dietary and lifestyle information was collected at recruitment. Cox proportional hazard models were used to examine associations between meat intake and risks of cardia and gastric noncardia cancers and esophageal adenocarcinoma. Data from a calibration substudy were used to correct hazard ratios (HRs) and 95% confidence intervals (CIs) for diet measurement errors. In a nested case-control study, we examined interactions between Helicobacter pylori infection status (i.e., plasma H. pylori antibodies) and meat intakes. All statistical tests were two-sided. Results: During a mean follow-up of 6.5 years, 330 gastric adenocarcinoma and 65 esophageal adenocarcinomas were diagnosed. Gastric noncardia cancer risk was statistically significantly associated with intakes of total meat (calibrated HR per 100-g/ day increase = 3.52; 95% CI = 1.96 to 6.34), red meat (calibrated HR per 50-g/day increase = 1.73; 95% CI = 1.03 to 2.88), and processed meat (calibrated HR per 50-g/day increase = 2.45; 95% CI = 1.43 to 4.21). The association between the risk of gastric noncardia cancer and total meat intake was especially large in H. pylori-infected subjects (odds ratio per 100-g/day increase = 5.32; 95% CI = 2.10 to 13.4). Intakes of total, red, or processed meat were not associated with the risk of gastric cardia cancer. A positive but non-statistically significant association was observed between esophageal adenocarcinoma cancer risk and total and processed meat intake in the calibrated model. In this study population, the absolute risk of development of gastric adenocarcinoma within 10 years for a study subject aged 60 years was 0.26% for the lowest quartile of total meat intake and 0.33% for the highest quartile of total meat intake. Conclusion: Total, red, and processed meat intakes were associated with an increased risk of gastric noncardia cancer, especially in H. pylori antibody-positive subjects, but not with cardia gastric cancer.

Cardiac rehabilitation (CR) is very effective for secondary prevention of cardiovascular disorders. The objective of this study was to analyze population factors associated with nonenrollment of cardiac patients in these programs.

Estimar la prevalencia de la lactancia materna exclusiva en la cohorte INMA (Infancia y Medio Ambiente) de Guipúzcoa durante los primeros 6 meses de vida del bebé. Identificar las razones de su abandono y determinar los factores asociados.

It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype-specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed significant increased risks of CLL (n = 102) with increasing mtDNA copy number (odds ratio = 1.34, 1.44, and 1.80 for quartiles 2-4, respectively; Ptrend = .001). mtDNA copy number was not associated with follow-up time, suggesting that this observation is not strongly influenced by indolent disease status. This study substantially strengthens the evidence that mtDNA copy number is related to risk of CLL and supports the importance of mitochondrial dysfunction as a possible mechanistic pathway in CLL ontogenesis.

Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death.

Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants.

Social position has yet to be established as a risk factor of coronary heart disease (CHD). Our aim was to investigate an individual life-course social position gradient link with CHD incidence in the EPIC-Spain cohort.41,066 participants, mostly 30–65 years old, and free of cardiovascular disease at baseline (1992–1996) were followed up for a mean of 10.4 years. A combined score of paternal occupation in childhood and own adult education was used to assess individual life-course risk accumulation. Hazard ratios of CHD were estimated using Cox models, stratifying by centre, and age, and adjusting for cardiovascular risk factors.583 participants (80 % men) developed a definite CHD event. Paternal occupational class IV was associated with CHD in all models in men. The educational gradient remained significant after adjusting for diet and physical activity (p= 0.01). All adjusted risk of incident CHD rose by 23 % (95 % CI 6–42 %) per category increase of life-course social position score in men. No significant associations were found in women.Individual life-course social position gradient was adversely related to incident CHD in Spanish men.

Large-scale prospective epidemiological data testing the association between physical activity (PA) and cerebrovascular diseases (CVDs) are scarce, particularly in Europe. The objective was to assess the risk of CVD according to PA levels in adults.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 32P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (1.87 μmol GSH g−1haemoglobin, p 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

There is uncertainty regarding the association of occupational exposures with lung cancer. We have studied the association between 52 high-risk job titles and lung cancer incidence in a large prospective study, with more than 200,000 participants followed for more than 6 years and 809 incident cases of lung cancer.

The objective of the present study was to estimate the dietary intake of polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene (B[a]P), as well as to identify the principal dietary sources of such compounds in the Spanish adult population. The study included 40,690 subjects aged 35 to 64 years from five regions of Spain that were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Spain cohort. Usual food intake was estimated by personal interview through a computerized version of a dietary history questionnaire. The estimations of B[a]P and total PAHs were made, taking into account the country where the determinations of content of these compounds in the foods came from and the year of publication. The mean intake of B[a]P in the population was 0.14 μg/day, and the mean intake of total PAHs was 8.57 μg/day. Both for B[a]P and total PAHs, women had a significantly lower mean intake than men, and older people consumed lesser amounts than younger people. Furthermore, the intake was higher in the northern regions. There were no significant differences by smoking status. The food groups of meat and meat products, cereals, and oils and fats contribute 55.5% to the total B[a]P intake, while cereals and meat and meat products contribute 61% to the total PAH consumption. Our estimations of B[a]P intake were lower than in the United Kingdom and The Netherlands, were similar to those found in other studies from Spain and Italy, and were higher than those in the United States and Norway.

Three congeners of polychlorinated biphenyls (PCBs)—the 2, 2', 3, 4, 4', 5'-, 2, 2', 4, 4', 5, 5'-nexachloro, and 2, 2', 3, 4, 4', 5, 5'-heptachlorobiphenyls—were determined in 18 samples of butter, 44 of fish (hake and anchovy) and 24 of egg, all of which came from markets in Guipuzcoa. The total content as Araclor 1260 was also determined. Quantitation was carried out by gas chromatography in a capillary column and electron capture detector. The total content in butter ranged from 20 to 60 ng/g (fat basis), in fish from 10 to 250 ng/g (edible part), and in eggs from 1 to 10 ng/g (edible part). None of these exceeded the tolerance limits established by the Canadian Government Guideline and USFDA.

The prevalence of hepatitis A virus antibodies was studied using a commercial ELISA method. 2,214 subjects were included, 1,211 in 1992 and 1,003 during 1986-87. In 1992 the seroprevalence rates among subjects 1-9, 10-19, 20-29 and 30-39 years old were 2.4%, 21%, 57.6% and 87.5% respectively, as compared with 7.7%, 37.9%, 80.6% and 98.1% respectively, in a similar group of subjects studied 5 years earlier (p ≤ 0.001). The reported number of viral hepatitis cases declined from 35.0 per 100,000 people in 1984 to 8.9 per 100,000 in 1992. Concurrently, the age when contracting the disease rose. The mean age for patients acquiring hepatitis A was 15.5 in 1986-88 and 20.1 in 1991-92. The decline in incidence and prevalence of HAV infection indicates a progressive and continuous decrease in HAV circulation in this geographical area.

ObjectiveTo investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.DesignProspective case-cohort study.SettingPopulations from eight European countries.Participants9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measureIncident type 2 diabetes.ResultsIn a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.ConclusionsThese findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

IMPORTANCE: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. OBJECTIVE: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. EXPOSURES: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. MAIN OUTCOMES AND MEASURES: Invasive or in situ premenopausal breast cancer. RESULTS: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs &lt;17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor–positive and/or progesterone receptor–positive than for hormone receptor–negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor–positive and progesterone receptor–positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor–negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor–negative breast cancer overall. CONCLUSIONS AND RELEVANCE: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.

IMPORTANCE: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. OBJECTIVE: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. DESIGN, SETTING, AND PARTICIPANTS: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). MAIN OUTCOMES AND MEASURES: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). RESULTS: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model. CONCLUSIONS AND RELEVANCE: This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

OBJECTIVE: To assess the association between consumption of fried foods and risk of coronary heart disease. Design Prospective cohort study. Setting Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. Participants 40 757 adults aged 29-69 and free of coronary heart disease at baseline (1992-6), followed up until 2004. MAIN OUTCOME MEASURES: Coronary heart disease events and vital status identified by record linkage with hospital discharge registers, population based registers of myocardial infarction, and mortality registers. RESULTS: During a median follow-up of 11 years, 606 coronary heart disease events and 1135 deaths from all causes occurred. Compared with being in the first (lowest) quarter of fried food consumption, the multivariate hazard ratio of coronary heart disease in the second quarter was 1.15 (95% confidence interval 0.91 to 1.45), in the third quarter was 1.07 (0.83 to 1.38), and in the fourth quarter was 1.08 (0.82 to 1.43; P for trend 0.74). The results did not vary between those who used olive oil for frying and those who used sunflower oil. Likewise, no association was observed between fried food consumption and all cause mortality: multivariate hazard ratio for the highest versus the lowest quarter of fried food consumption was 0.93 (95% confidence interval 0.77 to 1.14; P for trend 0.98). CONCLUSION: In Spain, a Mediterranean country where olive or sunflower oil is used for frying, the consumption of fried foods was not associated with coronary heart disease or with all cause mortality.

OBJECTIVE: To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. MAIN OUTCOME MEASURES: Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. RESULTS: If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (–3 to 38%) for liver, 17% (10 to 25%) and 4% (–1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. CONCLUSIONS: In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. CONCLUSIONS: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

OBJECTIVE: To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. Design Multicentre, prospective cohort study. Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. MAIN OUTCOME MEASURES: Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. RESULTS: An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). CONCLUSION: The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.