Met160Val TMPRSS2 gene polymorphism and early onset prostate cancer in high-risk men

Abstract

5000 Background: The TMPRSS2-ERG gene fusion has been found in over 50% of prostate tumors and its role is being characterized in various clinical settings. The T-allele of the Met160Val single nucleotide polymorphism (SNP) has been found to be associated with translocation and multiple copies of the TMPRSS2-ERG fusion. This SNP needs clinical characterization in men at high risk for prostate cancer (PCA) (men with a family history [FH] of PCA and African American [AA] men) to determine the role in personalizing PCA early detection. The Prostate Cancer Risk Assessment Program (PRAP) is a prospective screening program for high risk men. PRAP has > 700 participants, and 60% are AA. Here we evaluated the Met160Val SNP (rs12329760) in the TMPRSS2 gene with respect to race, FH of PCA, and time to PCA diagnosis. Methods: Eligibility for PRAP includes men ages 35–69 years with one first degree relative with PCA, two second degree relatives with PCA on the same side of the family, any AA man regardless of FH of PCA, and men with BRCA1/2 mutations. Criteria for biopsy and biopsy approach have been reported previously. Genotyping of the Met160Val SNP was performed using the Taqman SNP Genotyping Assay (Applied Biosystems). Standard statistical methods were used to determine risk-genotype distributions. Cox models were used for time to PCA diagnosis by risk genotype. Results: Out of 700 men in PRAP, 631 were able to be genotyped for the Met160Val SNP. There was no difference in distribution of genotypes (CT/TT vs. CC) among 231 White men with familial PCA and 400 AA men in PRAP. Among 183 White men with familial PCA with > one follow-up visit, those with the CT/TT genotypes were found to have a significantly earlier time to PCA diagnosis vs. the CC genotype (p = 0.0058). In addition, the hazard ratio for PCA among high-risk White men of the CT/TT genotypes vs CC genotype was 2.55 (p = 0.022) after controlling for age and PSA. No trends were seen among AA men for time to PCA diagnosis for any of the Met160Val SNP genotypes. Conclusions: The T-allele of the Met160Val variant in the TMPRSS2 gene may be informative of time to PCA diagnosis among White men who have a FH of PCA. This genetic variant warrants further study in high-risk men with familial PCA for its role in personalizing PCA early detection. No significant financial relationships to disclose.