Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition.

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest.

Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study.

AIMS/HYPOTHESIS: We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. METHODS: The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. RESULTS: A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. CONCLUSIONS/INTERPRETATION: Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.

Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study.

BACKGROUND AND AIMS: Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components. METHODS AND RESULTS: With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study. Plasma phytosterol-to-cholesterol ratios were inversely associated with all components of the MetS. In the dyslipidemic group, multivariable analyses showed that a 1-SD increase in sitosterol-to-cholesterol ratio was associated with a reduced risk for any MetS feature, ranging from 0.57 (95% CI, 0.45 to 0.71) for visceral adiposity to 0.82 (95% CI, 0.69 to 0.98) for high blood pressure. The risk of having MetS was nearly halved, with ORs of 0.49 (95% CI, 0.38 to 0.64) or 0.56 (95% CI, 0.44-0.70), depending on the definition. Results were opposed for plasma lathosterol, a marker of cholesterol synthesis. Most findings were reproduced in the healthy cohort. ApoE genotype was unrelated to plasma noncholesterol sterols. CONCLUSION: In both dyslipidemic and healthy populations, MetS is associated with increased plasma lathosterol, a cholesterol synthesis marker, and decreased plasma sitosterol, a marker of cholesterol absorption. Elevated plasma phytosterols related to a lower frequency of cardiometabolic risk factors, suggesting that they are associated with a reduced CVD risk.

Smoking and lymphoma risk in the European prospective investigation into cancer and nutrition.

Lymphomas are one of the few cancers that have been increasing in incidence over the past decades. So far, only a few established risk factors have been identified, including immunosuppression and viral infections. Recent evidence suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may affect risk differently, depending on the lymphoma entity. The European Prospective Investigation into Cancer and Nutrition was used to study the role of smoking in the etiology of lymphomas and individual subtypes within a prospective study. Information on baseline and lifetime tobacco smoking by 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified. Relative risk for smokers at recruitment was more than twofold higher for Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In this prospective study, smoking appeared to increase Hodgkin's lymphoma risk consistently in both genders, whereas B-cell non-Hodgkin's lymphoma risk was not associated. Future analysis should involve viral biomarkers and genetic susceptibility markers to elucidate potential mechanisms of smoking-induced carcinogenesis, particularly for Hodgkin's lymphoma.

Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.

BACKGROUND/OBJECTIVES: Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D. SUBJECTS/METHODS: A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis. RESULTS: After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D. CONCLUSIONS: 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.

Variants in phospholipid metabolism and upstream regulators and non-small cell lung cancer susceptibility.

AIM: The relevance of the cytidine diphosphate-choline and Rho GTPases pathways in the pathogenesis of cancer has been previously demonstrated. We investigate by a case-control association study if genetics variants in these pathways are associated with risk of developing lung cancer. METHODS: Thirty-seven tag SNPs were evaluated as risk factor of NSCLC in 897 cases and 904 controls. RESULTS: Six SNPs were nominally associated with lung cancer risk, which were not significant after the Bonferroni correction for multiple comparisons. No association was observed with the remaining 31 analyzed SNPs, neither it was found significant in haplotype frequencies. CONCLUSIONS: Although the implication of the two pathways investigated in our study in carcinogenesis is well established, our null results suggest that common genetic variants in CDP-choline and Rho GTPases-related genes are not risk factors for lung cancer.

Anthropometric factors and risk of endometrial cancer: the European prospective investigation into cancer and nutrition.

OBJECTIVE: To examine the association between anthropometry and endometrial cancer, particularly by menopausal status and exogenous hormone use subgroups. METHODS: Among 223,008 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, there were 567 incident endometrial cancer cases during 6.4 years of follow-up. The analysis was performed with Cox proportional hazards modeling. RESULTS: Weight, body mass index (BMI), waist and hip circumferences and waist-hip ratio (WHR) were strongly associated with increased risk of endometrial cancer. The relative risk (RR) for obese (BMI 30- < 40 kg/m(2)) compared to normal weight (BMI < 25) women was 1.78, 95% CI = 1.41-2.26, and for morbidly obese women (BMI > or = 40) was 3.02, 95% CI = 1.66-5.52. The RR for women with a waist circumference of > or =88 cm vs. <80 cm was 1.76, 95% CI = 1.42-2.19. Adult weight gain of > or =20 kg compared with stable weight (+/-3 kg) increased risk independent of body weight at age 20 (RR = 1.75, 95% CI = 1.11-2.77). These associations were generally stronger for postmenopausal than premenopausal women, and oral contraceptives never-users than ever-users, and much stronger among never-users of hormone replacement therapy compared to ever-users. CONCLUSION: Obesity, abdominal adiposity, and adult weight gain were strongly associated with endometrial cancer risk. These associations were particularly evident among never-users of hormone replacement therapy.

[Vaccination of chickenpox in children with acute lymphoblastic leukaemia]. / Vacunación de varicela en niños con leucemia linfoblástica aguda.

Varicella vaccine has shown its efficacy to prevent the disease and complications in healthy and immunodeficient children. In this article the authors evaluate the immunologic status of acute lymphoblastic leukaemia at diagnosis and at follow up and the development of chickenpox and/or herpes zoster. Children with negative serology and continuous complete remission of acute lymphoblastic leukaemia for one year were vaccinated. Of 71 children diagnosed of acute lymphoblastic leukaemia from 1983 to 1996, 25 received the vaccine and seroconversion was obtained in 76% after one dose and 92% after the second dose. Vaccine tolerance was adequate. The incidence of herpes zoster infection was decreased in vaccinated children during chemotherapy compared to the wild-virus infected ones. Nowadays that vaccine for healthy children is recommended, we consider a priority to protect from chickenpox the children affected by leukaemia that are in continuous complete remission of the disease.