Genetic variability and prostate cancer

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, Grönberg H, Isaacs WB, Karlsson R, Wiklund F, Xu J, Allen NE, Andriole GL, Barricarte A, Boeing H, Bas Bueno-de-Mesquita H, 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, Spencer Feigelson H, Riboli E, Hunter DJ, Chanock SJ, Haiman CA, Kraft P. Genome-wide association study identifies new prostate cancer susceptibility loci. Hum Mol Genet. 2011 Oct 1;20(19):3867-75. Epub 2011 Jul 8.

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.

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