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  • BODY-MASS INDEX  (2)
  • GENOME-WIDE ASSOCIATION  (2)
Keywords
  • 1
    Keywords: RISK ; REPRODUCIBILITY ; PROSTATE-CANCER ; FUTURE ; EPIC-GERMANY ; CARDIOVASCULAR-DISEASE ; GENOME-WIDE ASSOCIATION ; D-BINDING PROTEIN ; CIRCULATING VITAMIN-D ; CASE-COHORT
    Abstract: Circulating 25-hydroxyvitamin D (25(OH)D) has been associated with cardiovascular disease (CVD) risk in observational studies. Also, SNPs to explain variation in 25(OH)D have been identified by genome-wide association studies. Detection of direct associations between SNPs that significantly affect 25(OH)D and CVD risk would indicate a causal role of vitamin D, as reverse causation could be excluded and confounding could be better controlled. Thus, a combined analysis of candidate SNPs in relation to circulating 25(OH)D and CVD risk was carried out. A case-cohort study within the EPIC-Germany study was conducted comprising a randomly drawn subcohort of 2,132 subjects (57.9% women, mean age: 50.6 years) and incident cases of myocardial infarction (n=559) and stroke (n=471) that occurred during a mean follow-up duration of 7.6 years. 25(OH)D concentrations were measured by LC-MS/MS in baseline plasma samples. Additionally, eight candidate SNPs were assayed. Associations between 25(OH)D, SNPs and the risks of myocardial infarction and stroke were assessed by multivariable regression analyses. Mean 25(OH)D level was 47.2 nmol/L in the subcohort. Four SNPs were associated with 25(OH)D (p〈0.05). In subjects with 25(OH)D levels 〈25 nmol/L, the risks of CVD as composite endpoint (Hazard Ratio: 1.53, 95% confidence interval: 1.12-2.09), myocardial infarction, and stroke were significantly increased compared to subjects with levels 〉/=50 nmol/L, while no significant linear associations were observed. A SNP score was not related to the risks of total CVD (Hazard Ratio: 1.0, 95% confidence interval: 0.71-1.42), myocardial infarction, or stroke. The same was true concerning single SNPs. Given the lack of association between SNPs and the risks of stroke and myocardial infarction, the present findings do not point to a major causal role of vitamin D in the development of these diseases. However, a detection of modest associations between genetic markers and CVD risk in larger consortia cannot be ruled out.
    Type of Publication: Journal article published
    PubMed ID: 23935930
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  • 2
    Keywords: PROSTATE-CANCER ; POSTMENOPAUSAL WOMEN ; EPIC PROJECT ; RELATIVE VALIDITY ; GENOME-WIDE ASSOCIATION ; GERMAN PART ; D DEFICIENCY ; D SUPPLEMENTATION ; D INSUFFICIENCY ; 25-HYDROXYVITAMIN D LEVELS
    Abstract: Considerable variation in 25-hydroxyvitamin D (25(OH)D) in populations worldwide that seems to be independent of latitude has been reported. Therefore, we aimed to assess vitamin D status of a mid-aged German general population and to identify its dietary, lifestyle, anthropometric, and genetic determinants. 25(OH)D concentrations were measured by LC-MS/MS in plasma samples of a random subcohort of the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) comprising 2,100 subjects aged 35-65 years. Associations between potential predictors and 25(OH)D were assessed by linear regression models. 32.8 % of the variance in 25(OH)D was explained by a multivariable regression model, with season being the by far strongest predictor (semi-partial R (2): 14.6 %). Sex, waist circumference, leisure time physical activity, smoking, polymorphisms in the GC, CYP2R1, and DHCR7 genes, supplement use, exogenous hormone use, alcohol consumption, egg consumption, and fish consumption were significantly associated with 25(OH)D concentrations as well. However, none of these factors explained 〉 2.3 % of the variance in 25(OH)D. Even with a comprehensive set of genetic, anthropometric, dietary, and lifestyle correlates, not more than 32.8 % of the variation in 25(OH)D could be explained in the EPIC-Germany study, implying that vitamin D prediction scores may not provide an appropriate proxy for measured 25(OH)D. Food intake was only a weak predictor of 25(OH)D concentrations, while a strong seasonal fluctuation in 25(OH)D was shown.
    Type of Publication: Journal article published
    PubMed ID: 24005870
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  • 3
    Keywords: CANCER ; OBESITY ; ADIPOSE-TISSUE ; BINDING PROTEIN ; INSULIN-RESISTANCE ; BODY-MASS INDEX ; CARDIOVASCULAR RISK ; CYSTATIN C ; ADIPONECTIN LEVELS ; YOUNG MEN
    Abstract: Purpose To investigate whether blood-based biomarkers can improve the prediction of visceral fat volume as measured by magnetic resonance imaging (MRI) and thus be used as proxies of visceral adiposity in large-scale epidemiological studies. Methods Whole-body MRI was performed to determine overall and regional body compartments in 542 participants aged 48-80 years (52 % men) of the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. Anthropometric measures were taken, and clinical chemistry profiles including 15 routine biomarkers were obtained. Furthermore, nine novel biomarkers of visceral fat were assayed in a discovery sample of 100 participants. Multivariable regression models were calculated to assess associations between anthropometric variables, biomarkers, and visceral fat volume. Results The proportion of variance in visceral fat volume explained by anthropometric measures was 65.2 % in women and 60.8 % in men. By using blood-based biomarkers in addition to anthropometric indices, the variance in visceral fat volume explained could be increased by 4.8 % in women and 4.0 % in men. After backward selection, HbA1c, triglycerides, and adiponectin remained in the final multivariable regression model in women, while in men hsCRP, leukocytes, AST (GOT), GGT, LDL, and adiponectin remained in the final model. Conclusions In the present study, blood-based biomarkers moderately improved the prediction of visceral fat volume. This finding suggests that the underestimation of true associations between visceral fat and disease outcomes in epidemiological studies remains critical, even when using comprehensive sets of anthropometric and biomarker variables as proxies of visceral adiposity.
    Type of Publication: Journal article published
    PubMed ID: 25098781
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  • 4
    Keywords: DIAGNOSIS ; RISK ; BREAST-CANCER ; COLON-CANCER ; nutrition ; LIFE-STYLE FACTORS ; BODY-MASS INDEX ; REPRODUCTIVE HISTORY ; RECREATIONAL PHYSICAL-ACTIVITY ; RESEARCH FUND/AMERICAN INSTITUTE
    Abstract: BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend 〈0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
    Type of Publication: Journal article published
    PubMed ID: 25948112
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