Poster Sessions

BIOINFO-3

Charles Chung

C. Chung, J. Ciama, N. Chatterjee, M. Yeager, K. Jacobs, R. Hoover, D. Hunter, G. Thomas, S. Chanock

Fine-Mapping of the Prostate Cancer Locus on Chromosome 11q13 Reveals Three Independent Common Variants in CGEMS

Two recent genome-wide association studies (GWAS) have identified prostate cancer susceptibility alleles on chromosome 11q13. As part of the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative, the region flanking the most significant marker, rs10896449 on 11q13 was fine mapped for common single nucleotide polymorphisms (SNPs). The region was defined by a 0.2cM recombination map surrounding rs10896449. A two-staged tagging strategy was used to choose SNPs from HapMap phase 2. One hundred twenty SNPs passed quality control metrics and were analyzed in 10,272 cases and 9,123 controls, all of European origin, drawn from 10 studies. A combined joint adjusted analysis identified 18 SNPs below genome-wide significance (P < 1.0E-08); notably, rs10896449 remained the most significant (P=7.94x10-19). The associations of rs10896437, rs12793759, and rs10896449 remained significant after adjustment for each other (rs10896449, P=3.42E-09; rs12793759, P=6.73E-04; rs10896437, P=6.95E-03). We observed strong evidence for a recombination hotspot that separates rs10896437 from rs10896449 and rs12793759, which corroborates our finding of at least three independent signals. Our study has identified a more complex architecture underlying the common variants contributing to prostate cancer risk at 11q13. Further studies are required to investigate the biological basis of the observed multiple association signals.