Racial differences in prediction of time to prostate cancer diagnosis in a prospective screening cohort of high‐risk men: effect of TMPRSS2 Met160Val

Abstract

What’s known on the subject? and What does the study add? The TMPRSS2‐ERG fusion is a common gene fusion event in prostate tumours. Germline genetic variants that predict fusion in the tumour are under study. This study evaluates one germline genetic variant regarding predicting time to prostate cancer diagnosis among high‐risk men undergoing screening for prostate cancer. A specific genotype is associated with earlier time to prostate cancer diagnosis among Caucasian men with a family history of prostate cancer. The results suggest that such variants may be useful after further study in stratifying high‐risk men for individualized early detection approaches. INTRODUCTION To evaluate the TMPRSS2‐ERG gene polymorphism with respect to self‐identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high‐risk men. PATIENTS AND METHODS A total of 631 men aged between 35 and 69 years were studied. ‘High‐risk’ was defined as ≥ one first degree or two second degree relatives with PCA, any African American (AA) man regardless of familial PCA, and men with BRCA1/2 mutations. Men with elevated prostate‐specific antigen (PSA) concentrations or other indications for PCA underwent biopsy. Men were followed from time of study entry to PCA diagnosis. Cox models were used to evaluate time to PCA diagnosis by genotype. RESULTS Genotype distribution differed significantly by SIRE (CT/TT vs CC, P < 0.0001). Among 183 Caucasian men with at least one follow‐up visit, PCA was more than doubled in men carrying CT/TT vs CC genotypes (hazard ratio = 2.55, 95% CI = 1.14–5.70) after controlling for age and PSA. No association was seen among AA men by TMPRSS2 genotype. CONCLUSIONS The T‐allele of the Met160Val variant in TMPRSS2 , which has been associated with the TMPRSS2–ERG fusion, may be informative of time to PCA diagnosis for a subset of high‐risk Caucasian men who are undergoing regular PCA screening. This variant, along with other genetic markers, warrant further study for personalizing PCA screening.