Analysis of Ethnic Admixture in Prostate Cancer
Final rept. 30 Nov 2005-29 Nov 2007
WAYNE STATE UNIV DETROIT MI
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Evidence for a genetic component to prostate cancer is strong, however few genes have been identified, and most of the genetic risk remains undefined. To date, multiple traditional genome scans have been performed, and several susceptibility loci have been identified. Traditional genome scans using familial data have generally not included enough African Americans to provide adequate statistical power to detect linkage. Our project uses a novel approach to gene discovery with greater power to detect genetic effects, admixture mapping, to identify prostate cancer susceptibility loci in a sample of African American men. Freedman et al. reported a susceptibility region on chromosome 8q24, detected by admixture mapping in 1,597 African American men. In the current study, approximately 800 samples from 2 case-control study of prostate cancer were genotyped for ancestry informative markers across the genome. Admixture mapping analyses were performed using ADMIXMAP and ANCESTRYMAP statistical programs. The prostate cancer susceptibility locus on 8q24 identified by Freedman et al. was confirmed, with a peak lod score estimated using ANCESTRYMAP of 1.54 between markers rs12547950 and rs4367565. A new prostate cancer susceptibility locus on chromosome 5q35 was identified, with a maximum lod score of 3.16 detected at marker rs7729084 using ADMIXMAP. This new region is actively being explored via fine mapping and candidate gene approaches.
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