Association of Type 2 Diabetes Susceptibility Variants With Advanced Prostate Cancer Risk in the Breast and Prostate Cancer Cohort Consortium

作者：Mitchell J. Machiela, Sara Lindström, N. E. Allen, C. A. Haiman, Demetrius Albanes, Aurelio Barricarte, Sonja I. Berndt, H. Bas Bueno‐de‐Mesquita, Stephen J. Chanock, J. Michael Gaziano, Susan M. Gapstur, Edward L. Giovannucci, Brian E. Henderson, Eric J. Jacobs, Laurence N. Kolonel, Vittorio Krogh, Jing Ma, M. J. Stampfer, Victoria L. Stevens, D. O. Stram, Anne Tjønneland, R.C. Travis, W. C. Willett, D. J. Hunter, L. Le Marchand, Peter Kraft · 发表于：American Journal of Epidemiology · 年份：2012 · DOI：10.1093/aje/kws191 · 被引用次数：82 · 研究领域：Genetic Associations and Epidemiology、Metabolism, Diabetes, and Cancer、RNA modifications and cancer

Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases.