Iron has been suggested as a risk factor for different types of cancers mainly due to its prooxidant activity, which can lead to oxidative DNA damage. Furthermore, subjects with hemochromatosis or iron overload have been shown to have a higher risk of developing liver cancer. We have systematically reviewed 59 epidemiologic studies, published between 1995 and 2012, reporting information on total iron, dietary iron, heme iron, and biomarkers of iron status and cancer risk. Furthermore we conducted metaanalysis for colorectal [relative risk (RR), 1.08; 95% confidence interval (CI), 1.00-1.17], colon (RR ¼ 1.12; 95% CI, 1.03-1.22), breast (RR ¼ 1.03; 95% CI, 0.97-1.09), and lung cancer (RR ¼ 1.12; 95% CI, 0.98-1.29), for an increase of 1 mg/day of heme iron intake. Globally, on the basis of the systematic review and the metaanalysis results, a higher intake of heme iron has shown a tendency toward a positive association with cancer risk. Evidence regarding high levels of biomarkers of iron stores (mostly with serum ferritin) suggests a negative effect toward cancer risk. More prospective studies combining research on dietary iron intake, iron biomarkers, genetic susceptibility, and other relevant factors need to be conducted to clarify these findings and better understand the role of iron in cancer development. Cancer Epidemiol Biomarkers Prev; 23(1); 12-31. Ó2013 AACR.

OBJECTIVEYounger age at menarche, a marker of pubertal timing in girls, is associated with higher risk of later type 2 diabetes. We aimed to confirm this association and to examine whether it is explained by adiposity.RESEARCH DESIGN AND METHODSThe prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 individuals from 26 research centers across eight European countries. We tested the association between age at menarche and incident type 2 diabetes using Prentice-weighted Cox regression in 15,168 women (n = 5,995 cases). Models were adjusted in a sequential manner for potential confounding and mediating factors, including adult BMI.RESULTSMean menarcheal age ranged from 12.6 to 13.6 years across InterAct countries. Each year later menarche was associated with 0.32 kg/m2 lower adult BMI. Women in the earliest menarche quintile (8–11 years, n = 2,418) had 70% higher incidence of type 2 diabetes compared with those in the middle quintile (13 years, n = 3,634), adjusting for age at recruitment, research center, and a range of lifestyle and reproductive factors (hazard ratio [HR], 1.70; 95% CI, 1.49–1.94; P < 0.001). Adjustment for BMI partially attenuated this association (HR, 1.42; 95% CI, 1.18–1.71; P < 0.001). Later menarche beyond the median age was not protective against type 2 diabetes.CONCLUSIONSWomen with history of early menarche have higher risk of type 2 diabetes in adulthood. Less than half of this association appears to be mediated by higher adult BMI, suggesting that early pubertal development also may directly increase type 2 diabetes risk.

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case–control subset (Ncases = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin‐like growth factor (IGF)‐I levels. For cohort analyses, multivariable‐adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case–control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed‐up for an average of 11 years (person‐years follow‐up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13–2.43; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02–2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02–2.38; ptrend = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65–1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case–control study, similar results were observed among hepatitis‐free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration.

Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity (PA) could promote weight loss/maintenance and be important determinants of breast cancer (BC) prognosis. The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes. This single-arm pre-post study, which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered to overweight and obese BC survivors shortly after treatment. Before and after the intervention, anthropometry, dietary information, quality of life (QoL) and cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were invited to participate: 42 of them started the intervention and 37 completed it. Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg, as well as significant decreases in body mass index, fat mass and waist circumference. Significant decreases in total energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %) intakes were observed while QoL and CRF showed significant increases. This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors. Assessing the long-term effects of these changes, and in particular their possible impact of BC prognosis, and designing interventions reaching a wider number of BC survivors are still issues to be addressed.

Background: We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival.Methods: Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 AE 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer-specific death (n ¼ 1,028) and all-cause death (n ¼ 1,525) for different quartiles of intake.Results: The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97-1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98-1.36). Multivariable-adjusted HRs for colorectal cancer-specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99-1.48) for milk, 1.09 (95% CI, 0.88-1.34) for yoghurt, and 0.93 (95% CI, 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer-specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81-1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84-1.21).Conclusions: The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer.Impact: The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival. Cancer Epidemiol Biomarkers Prev; 23(9); 1813-23. Ó2014 AACR.

The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self‐reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow‐up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC‐participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross‐sectional association between circulating concentrations of androgens and insulin‐like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63–0.86). There was no evidence that the association differed by stage (p‐heterogeneity, 0.19) or grade (p‐heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin‐like growth factor binding protein‐three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self‐reported diabetes mellitus and subsequent risk of prostate cancer.

Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow‐up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center‐specific questionnaires. Heme iron was calculated as a type‐specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05–2.68 and HR: 2.27, 95% CI:1.33–3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC.

Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.