Abstract 4725: Interrogating region 4 of 8q24.13 for prostate cancer risk in African Americans

In the USA, African American (AA) men are at higher risk of developing and dying from prostate cancer (Pca). Strong and replicable associations between prostate cancer risk and regions 1, 2, and 3 of 8q24 among cohorts of European ancestry have been found but few for those of African ancestry. Recently, we discovered in a study of AAs, a fourth region of Pca risk at 126 Mb of 8q24.13 surrounding SNP rs7008482. Region 4 is 2 Mb upstream of the other three regions on 8q24 and contains two interesting candidate genes for Pca risk. To further interrogate region 4, we performed fine-mapping within a 500-Kb region (126.1Mb-126.6Mb). SNPs were selected for fine-mapping of the region based on the following characteristics: tagging SNPs from Yoruba HAPMAP data and non-synonymous or potential regulatory SNPs. We genotyped 250 SNPs in 263 AA Pca cases and 562 AA healthy controls. A structured-association analysis taking into account African ancestry, (local 8q24 ancestry and genomic ancestry) revealed that several SNPs within two genes KIAA0196 and NSMCE2 were significantly associated with Pca risk. The majority of the associated SNPs were common and exhibited low to moderate risk which may contribute to high population attributable risk in African Americans. Among these, rs16900305, located in an intronic region of KIAA0196, exhibited the strongest association (P=0.0003). KIAA0196 has been shown to be over-expressed in clinical prostate carcinomas and in approximately 30% of hormone-refractory tumors. Our findings strongly support region 4 in 8q24.13 as a candidate locus influencing prostate cancer risk among African Americans. Given the two interesting genes in this region and strong associations in a high risk group for Pca, further attention to this region is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4725.