prostate cancer susceptibility loci identified on chromosome 12 in african americans前列腺癌易感性位点确定12号染色体上的非洲裔美国人.pdfVIP

Prostate Cancer Susceptibility Loci Identified on Chromosome 12 in African Americans 1 2 3 4 2¤ Carolina Bonilla *, Stanley Hooker , Tshela Mason , Cathryn H. Bock , Rick A. Kittles 1 School of Social and Community Medicine, University of Bristol, Bristol, Avon, United Kingdom, 2 Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America, 3 National Human Genome Center at Howard University, Washington, D. C., United States of America, 4 Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America Abstract Prostate cancer (PCa) is a complex disease that disproportionately affects African Americans and other individuals of African descent. A number of regions across the genome have been associated to PCa, most of them with moderate effects. A few studies have reported chromosomal changes on 12p and 12q that occur during the onset and development of PCa but to date no consistent association of the disease with chromosome 12 polymorphic variation has been identified. In order to unravel genetic risk factors that underlie PCa health disparities we investigated chromosome 12 using ancestry informative markers (AIMs), which allow us to distinguish genomic regions of European or West African origin, and tested them for association with PCa. Additional SNPs were genotyped in those areas where significant signals of association were detected. The strongest signal was discovered at the SNP r located upstream of the PAWR gene, a tumor suppressor, which is amply expressed in the prostate. The most frequent allele in Europeans was the risk allele among African Americans. We also examined vitamin D related genes, VDR and CYP27B1, and found a signif