The relationship between dietary magnesium intake, stroke and its major risk factors, blood pressure and cholesterol, in the EPIC-Norfolk cohort.

BACKGROUND: Dietary magnesium could modify the major stroke risk factors, high blood pressure (BP) and cholesterol, but has been understudied in both sexes in a single population. This study aimed to investigate if dietary magnesium intake was associated with BP, total cholesterol (TC) and incident stroke risk in an adult population. METHODS: We conducted cross-sectional analyses in a case-cohort study of 4443, men and women aged 40-75, representative of 25,639 participants years of the EPIC (European Prospective Investigation into Cancer)-Norfolk cohort. The cohort included 928 stroke cases (42,556.5 person years). Dietary data from 7 day food diaries were analysed using multivariate regression to assess associations between quintiles or data-derived categories of dietary magnesium intake and BP, TC and stroke risk, adjusted for relevant confounders. RESULTS: We observed differences of -7 mmHg systolic BP (P trend ≤ 0.01) and -3.8 mmHg diastolic BP (P trend=0.01) between extreme intakes of magnesium in men, a significant inverse association with TC was observed (P trend=0.02 men and 0.04 women). Compared to the bottom 10%, the top 30% of magnesium intake was associated with a 41% relative reduction in stroke risk (HR 0.59; 95% CI 0.38-0.93) in men. CONCLUSIONS: Lower dietary magnesium intake was associated with higher BP and stroke risk, which may have implications for primary prevention.This study is supported by a University of East Anglia FMH studentship and, in Cambridge, by programme grants from the Medical Research Council UKG0401527 and Cancer Research UK (C864/A2883, C864/A8257).This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S016752731501270X

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Background: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). Methods and results: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (. P-value for heterogeneity=0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. Conclusions: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD

Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study.

BACKGROUND: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. RESULTS: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). CONCLUSIONS: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death

Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC

PURPOSE: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression. RESULTS: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade. CONCLUSION: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1,072 cases of lymphoid malignancies and 1,072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI = 0.57-1.03], ptrend  = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (pheterogeneity for all  ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes.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), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy 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), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A11692, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)

Characteristics of Medical Research News Reported on Front Pages of Newspapers

Background: The placement of medical research news on a newspaper's front page is intended to gain the public's attention, so it is important to understand the source of the news in terms of research maturity and evidence level. Methodology/Principal Findings: We searched LexisNexis to identify medical research reported on front pages of major newspapers published from January 1, 2000 to December 31, 2002. We used MEDLINE and Google Scholar to find journal articles corresponding to the research, and determined their evidence level. Of 734 front-page medical research stories identified, 417 (57%) referred to mature research published in peer-reviewed journals. The remaining 317 stories referred to preliminary findings presented at scientific or press meetings; 144 (45%) of those stories mentioned studies that later matured (i.e. were published in journals within 3 years after news coverage). The evidence-level distribution of the 515 journal articles quoted in news stories reporting on mature research (3% level I, 21% level II, 42% level III, 4% level IV, and 31% level V) differed from that of the 170 reports of preliminary research that later matured (1%, 19%, 35%, 12%, and 33%, respectively; chi-square test, P = .0009). No news stories indicated evidence level. Fewer than 1 in 5 news stories reporting preliminary findings acknowledged the preliminary nature of their content. Conclusions/Significance: Only 57% of front-page stories reporting on medical research are based on mature research, which tends to have a higher evidence level than research with preliminary findings. Medical research news should be clearly referenced and state the evidence level and limitations to inform the public of the maturity and quality of the source. © 2009 Lai, Lane.published_or_final_versio

Circulating insulin-like growth factor I in relation to melanoma risk in the European Prospective Investigation into Cancer and Nutrition

Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma

Fatty Acid Biomarkers of Dairy Fat Consumption and Incidence of Type 2 Diabetes: A Pooled Analysis of Prospective Cohort Studies

Background We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance±weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohortspecific 10th to 90th percentile range of 15:0 was 0.80 (0.73±0.87); of 17:0, 0.65 (0.59± 0.72); of t16:1n7, 0.82 (0.70±0.96); and of their sum, 0.71 (0.63±0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction \u3c 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. Conclusions In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D

Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant

Objective: Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. Research Design and Methods: We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. Results: We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: −0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: −0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. Conclusions: Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels