Genome-wide association study identifies new prostate cancer susceptibility loci

Schumacher FR, Berndt SI, Siddiq A, Jacobs KB, Wang Z, Lindstrom S, Stevens VL, Chen C, Mondul AM, Travis RC, Stram DO, Eeles RA, Easton DF, Giles G, Hopper JL, Neal DE, Hamdy FC, Donovan JL, Muir K, Al Olama AA, Kote-Jarai Z, Guy M, Severi G, Gronberg H, Isaacs WB, Karlsson R, Wiklund F, Xu J, Allen NE, Andriole GL, Barricarte A, Boeing H, Bueno-de-Mesquita HB, Crawford ED, Diver WR, Gonzalez CA, Gaziano JM, Giovannucci EL, Johansson M, Le Marchand L, Ma J, Sieri S, Stattin P, Stampfer MJ, Tjonneland A, Vineis P, Virtamo J, Vogel U, Weinstein SJ, Yeager M, Thun MJ, Kolonel LN, Henderson BE, Albanes D, Hayes RB, Feigelson HS, Riboli E, Hunter DJ, Chanock SJ, Haiman CA, Kraft P (2011) Genome-wide association study identifies new prostate cancer susceptibility loci. Hum Mol Genet 20:3867-3875

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" x="" 10(-8)).="" we="" also="" confirmed="" a="" locus="" suggested="" by="" an="" earlier="" gwas="" at="" 12q13="" (rs902774,="" p="8.6" x="" 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="">