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  • DKFZ Publication Database  (2)
  • DISEASE  (1)
  • ENDOGENOUS SEX-HORMONES  (1)
  • RENIN-ANGIOTENSIN SYSTEM  (1)
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  • DKFZ Publication Database  (2)
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  • 1
    Keywords: DISEASE ; kidney ; TRIAL ; HEALTH ; OUTCOMES ; METAANALYSIS ; RENIN-ANGIOTENSIN SYSTEM ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIANTS ; D SUPPLEMENTATION
    Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH) D concentration was associated with decreased systolic blood pressure (beta per 10% increase, -0.12 mm Hg, 95% CI -0.20.to -0.04; p=0.003) and reduced odds of hypertension (odds ratio [OR] 0.98, 95% CI 0.97-0.99; p=0.0003), but not with decreased diastolic blood pressure (beta per 10% increase, -0.02 mm Hg, -0.08 to 0.03; p=0.37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0.10 mm Hg in systolic blood pressure (-0.21 to -0.0001; p=0.0498) and a change of -0.08 mm Hg in diastolic blood pressure (-0.15 to -0.02; p=0.01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0.98, 0.96-0.99; p=0.001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH) D concentration was associated with a change of -0.29 mm Hg in diastolic blood pressure (-0.52 to -0.07; p=0.01), a change of -0.37 mm Hg in systolic blood pressure (-0.73 to 0.003; p=0.052), and an 8 1% decreased odds of hypertension (OR 0.92, 0.87-0.97; p=0.002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
    Type of Publication: Journal article published
    PubMed ID: 24974252
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  • 2
    Keywords: GROWTH ; MORTALITY ; ASSOCIATION ; VARIANTS ; TRIAL ; METAANALYSIS ; TESTOSTERONE ; MULTIETHNIC COHORT ; ENDOGENOUS SEX-HORMONES ; METFORMIN
    Abstract: 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. What's new? Emerging evidence suggests that men with type 2 diabetes are at lower risk to develop prostate cancer. Using data obtained within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors show that the prostate cancer risk was, indeed, reduced by 26% in men with type 2 diabetes but no association with cancer stage or grade was observed. In a subset of men for whom data on circulating hormones were available, levels of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in those with diabetes as compared to those without diabetes, giving clues to how having diabetes could affect prostate cancer development.
    Type of Publication: Journal article published
    PubMed ID: 24862312
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