Association of testis derived transcript gene variants and prostate cancer risk.

Abstract

The testis derived transcript gene has been suggested as a tumor suppressor gene for prostate cancer at 7q31. To investigate this concept we evaluated the effects of 7 tagging single nucleotide polymorphisms that comprehensively captured the common genetic variants in TES on aggressive prostate cancer in a case-control study. A total of 506 cases diagnosed with aggressive prostate cancer, and an equal number of age, institute and ethnicity matched controls, were recruited from the major medical institutions in Cleveland, Ohio. A logistic regression model was used to evaluate the association between SNPs/multimarker haplotypes and prostate cancer. When looking at all study subjects and white men only, no statistically significant associations were observed between any variants and more aggressive disease. However, 3 variants showed inverse associations with disease in black men (178), including 2 intronic SNPs (rs2402056, rs1004109) and 1 SNP close to the 3' untranslated region (rs4730721) with ORs of 0.57 (95% CI 0.36-0.90, under an additive mode of inheritance), 0.57 (95% CI 0.36-0.91, under an additive mode of inheritance) and 0.45 (95% CI 0.21-0.98, under a dominant mode of inheritance), respectively. Variants rs2402056 and rs1004109 are in tight linkage disequilibrium (r2=0.8) and the reconstructed haplotype did not provide any additional evidence for association than their genotype level results. Our findings suggest that the variants in TES, or in a nearby gene, may be associated with prostate cancer in black men.