Genetic Polymorphisms in Genes Involved in Inflammation and Prostate Cancer Risk

Abstract

Abstract : A recent hypothesis suggests a link between chronic inflammation within the prostate and the development and progression of prostate cancer (PCa). Inflammation in the prostate is common and takes many forms including prostatitis, proliferative inflammatory atrophy (PIA), and elevated markers of inflammation, such as interleukin-6. Prior literature suggests that cancer risk increases in the presence of chronic injury to tissues, as can result from chronic inflammation. Indeed, prostate cells affected by inflammation, e.g., PIA, show changes in their DNA similar to those seen in prostatitic intraepithelial neoplasia, a potential pre-cancerous lesion, and in PCa itself. This study aims to test the hypothesis that SNP alleles of selected inflammation-related genes increase risk of PCa. A second aim is to determine the role of SNPs in these genes on risk of developing more aggressive forms of PCa. The third aim is to explore the role of these alleles on risk of dying of PCa. At present, men from two population-based case-control studies in King County, Washington have been genotyped for 146 SNPs in fourteen candidate genes. Cases were diagnosed between January 1, 1993 and December 31, 1996 and between January 1, 2002 and December 31, 2005, respectively. Genotyping has been completed for 1,457 cases and 1,351 controls, with 141 of 146 SNPs successfully genotyped with 95% completeness and 99% agreement between blind duplicates. Hardy-Weinberg equilibrium has been calculated for all SNPs and linkage disequilibrium statistics (D' and r2) have been calculated for all SNPs within the same gene. Preliminary analyses are under way and odds ratios, adjusted for age alone, have been calculated for each SNP as an estimate of the association between the SNP genotypes and risk of prostate cancer.