Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease

Teerlink CC, Thibodeau SN, McDonnell SK, Schaid DJ, Rinckleb A, Maier C, Vogel W, Cancel-Tassin G, Egrot C, Cussenot O, Foulkes WD, Giles GG, Hopper JL, Severi G, Eeles R, Easton D, Kote-Jarai Z, Guy M, Cooney KA, Ray AM, Zuhlke KA, Lange EM, Fitzgerald LM, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Isaacs WB, Wahlfors T, Tammela T, Schleutker J, Wiklund F, Gronberg H, Emanuelsson M, Carpten J, Bailey-Wilson J, Whittemore AS, Oakley-Girvan I, Hsieh CL, Catalona WJ, Zheng SL, Jin G, Lu L, Xu J, International Consortium for Prostate Cancer G, Camp NJ, Cannon-Albright LA (2014) Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease. Hum Genet 133:347-356

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p