Abstract A66: Admixture and fine mapping in African Americans identifies a susceptibility locus for prostate cancer on chromosome 7.

Abstract

Abstract Background: There are well documented racial disparities in prostate cancer among African American (AA) men in the United States. AA men have a 60% higher incidence rate and over twice the mortality rate of Caucasian men. A previous admixture mapping study identified a region on chromosome 7 where excess European ancestry was associated with increased prostate cancer risk (Bock et al., 2009). Fine mapping of this region was performed to further identify prostate cancer susceptibility loci. Methods: DNA from 420 prostate cancer cases and 244 controls from Henry Ford Hospital in Detroit, MI and Howard University in Washington, DC was genotyped using an Illumina 1M chip. After quality control exclusions, 54,105 single-nucleotide polymorphisms (SNPs) on chromosome 7 were available for this analysis. Local ancestry was estimated using the Local Ancestry in adMixed Populations (LAMP) program, with ancestral allele frequencies obtained from HapMap. Admixture linkage was confirmed using an affected-only test. Fine-mapping within the region was conducted using the MIX-score method proposed by Pasaniuc et al. (2011) to identify the SNP(s) most likely to explain the admixture linkage. Results: The admixture linkage signal spanned from 7q31.1 (112.27Mb) to 7q34 (137.90Mb). Within this region, there were three SNPs with MIX-score p-values less than the Bonferonni corrected significance threshold. The highest level of significance was attained at SNP rs13221538 (p=1.16*10-7). This SNP is located in an intron of the Cadherin-like and PC-esterase domain-containing protein 1 (CPED1) gene. Adjusting for local ancestry, the allelic odds ratio for this SNP was 1.52 (p=1.16*10-5), and the C allele of this SNP is more prevalent in the Northern and Western European population (CEU - 82%) than in the West African population (YRI – 60%). While little is known about the function of CPED1, it is located between genes WNT16 and ING3. WNT16 is known to be involved in oncogenesis, and the WNT pathway has been implicated in b-catenin signaling and prostate cancer development. Conclusion: Utilizing admixture linkage information, association fine mapping has narrowed the region on chromosome 7q associated with prostate cancer risk and identified potential candidate SNPs likely to explain the observed admixture. Citation Format: Julie J. Ruterbusch, Albert M. Levin, Rick Kittles, Benjamin A. Rybicki, Cathryn H. Bock. Admixture and fine mapping in African Americans identifies a susceptibility locus for prostate cancer on chromosome 7. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A66.