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  • INSULIN-RESISTANCE  (3)
  • BREAST-CANCER  (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: BREAST-CANCER ; chemotherapy ; NON-HODGKINS-LYMPHOMA ; HEMATOLOGICAL MALIGNANCIES ; YOUNG-PATIENTS ; CHILDHOOD-CANCER SURVIVORS ; PREMATURE MENOPAUSE ; ANTI-MULLERIAN HORMONE ; GONADAL-FUNCTION ; INHIBIN-B
    Abstract: BACKGROUND: Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast cancer or Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment. RESULTS: A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P 〈 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population. CONCLUSION: Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.
    Type of Publication: Journal article published
    PubMed ID: 25962442
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  • 4
    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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  • 5
    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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  • 6
    Keywords: RECEPTOR ; EXPRESSION ; TYROSINE KINASE ; EPIDEMIOLOGY ; colon ; nutrition ; RECTAL-CANCER ; INSULIN-RESISTANCE ; MENDELIAN RANDOMIZATION ; INSTRUMENTS
    Abstract: Fetuin-A, also referred to as alpha2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 microg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 microg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
    Type of Publication: Journal article published
    PubMed ID: 25611809
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  • 7
    Keywords: CANCER ; RISK ; ASSOCIATION ; HUMANS ; nutrition ; INSULIN-RESISTANCE ; metabolic syndrome ; WOMENS HEALTH ; FISH INTAKE ; DAIRY CONSUMPTION
    Abstract: OBJECTIVE: The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: The 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 eight European countries, with an average follow-up time of 12.0 years. Pooled country-specific hazard ratios (HRs) and 95% CI of prentice-weighted Cox regression analyses were used to estimate type 2 diabetes incidence according to protein intake. RESULTS: After adjustment for important diabetes risk factors and dietary factors, the incidence of type 2 diabetes was higher in those with high intake of total protein (per 10 g: HR 1.06 [95% CI 1.02-1.09], Ptrend 〈 0.001) and animal protein (per 10 g: 1.05 [1.02-1.08], Ptrend = 0.001). Effect modification by sex (P 〈 0.001) and BMI among women (P 〈 0.001) was observed. Compared with the overall analyses, associations were stronger in women, more specifically obese women with a BMI 〉30 kg/m(2) (per 10 g animal protein: 1.19 [1.09-1.32]), and nonsignificant in men. Plant protein intake was not associated with type 2 diabetes (per 10 g: 1.04 [0.93-1.16], Ptrend = 0.098). CONCLUSIONS: High total and animal protein intake was associated with a modest elevated risk of type 2 diabetes in a large cohort of European adults. In view of the rapidly increasing prevalence of type 2 diabetes, limiting iso-energetic diets high in dietary proteins, particularly from animal sources, should be considered.
    Type of Publication: Journal article published
    PubMed ID: 24722499
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