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Sökning: WFRF:(Kampman E) > (2015-2019) > Brenner Hermann

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1.
  • Berendsen, A. A. M., et al. (författare)
  • Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults: A Meta-Analysis within the CHANCES Consortium
  • 2017
  • Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 43:3-4, s. 215-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged >= 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action [SENECA], Rotterdam Study [RS], Nurses' Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono-and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI -0.01, 0.02) in NHS, 0.00 (95% CI -0.02, 0.01) in RS, and 0.00 (95% CI -0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI -0.01, 0.01), I-2 = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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2.
  • Bien, Stephanie A., et al. (författare)
  • Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
  • 2019
  • Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 138:4, s. 307-326
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n=169) and whole blood (n=922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-4)). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P<0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.
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3.
  • Ordóñez-Mena, José Manuel, et al. (författare)
  • Quantification of the smoking-associated cancer risk with rate advancement periods : meta-analysis of individual participant data from cohorts of the CHANCES consortium
  • 2016
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
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