FR Schumacher, SI Berndt, A Siddiq, KB Jacobs, Z Wang, S Lindstrom, VL Stevens, C Chen, AM Mondul, RC Travis, DO Stram, RA Eeles, DF Easton, G Giles, JL Hopper, DE Neal, FC Hamdy, JL Donovan, K Muir, AA Al Olama, Z Kote-Jarai, M Guy, G Severi, H Grönberg, WB Isaacs, R Karlsson, F Wiklund, J Xu, NE Allen, GL Andriole, A Barricarte, H Boeing, HB Bueno-de-Mesquita, ED Crawford, WR Diver, CA Gonzalez, JM Gaziano, EL Giovannucci, M Johansson, L Le Marchand, J Ma, S Sieri, P Stattin, MJ Stampfer, A Tjonneland, P Vineis, J Virtamo, U Vogel, SJ Weinstein, M Yeager, MJ Thun, LN Kolonel, BE Henderson, D Albanes, RB Hayes, HS Feigelson, E Riboli, DJ Hunter, SJ Chanock, CA Haiman, P Kraft
Hum Mol Genet
Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.