ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2013
Pleiotropy between genetic markers of obesity and risk of prostate cancer.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 4 citations in OpenAlex.
- Association Analysis between Body Mass Index and Genomic DNA Methylation across 15 Major Cancer Types.Journal of Cancer · 2018Article
- The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium.Cancer causes & control : CCC · 2015Article
- Genetic Determinants of Metabolism and Benign Prostate Enlargement: Associations with Prostate Volume.PloS one · 2015Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTo address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer and genetic markers of obesity and metabolism.
methodsAnalyses included 176,520 single-nucleotide polymorphisms (SNP) associated with 23 metabolic traits. We examined the association between SNPs and prostate cancer in 871 cases and 906 controls, including 427 high-grade cases with Gleason ≥ 7. Genetic risk scores (GRS) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR.
resultsProstate cancer was associated with five loci, including cyclin M2, with P values less than 1 × 10(-4). In addition, the WHR GRS was associated with high-grade prostate cancer versus controls [OR, 1.05; 95% confidence interval (CI), 1.00-1.11; P = 0.048] and high-grade prostate cancer versus low-grade prostate cancer (OR, 1.07; 95% CI, 1.01-1.13; P = 0.03). None of these findings exceeds the threshold for significance after correction for multiple testing.
conclusionsVariants in genes known to be associated with metabolism and obesity may be associated with prostate cancer. We show evidence for pleiotropy between WHR GRS and prostate cancer grade. This finding is consistent with the function of several WHR genes and previously described relationships with cancer traits. IMPACT: Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in prostate cancer. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds within our sample size, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples.
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