TMPRSS2 rs12329760 variant as a prognostic marker for prostate cancer progression

TMPRSS2, a transmembrane serine protease and common partner in oncogenic TMPRSS2-ERG fusions, is regulated by androgen receptors and is implicated in prostate tumorigenesis. The nonsynonymous SNP rs12329760 (C > T; Val160Met) has been hypothesized to alter TMPRSS2 proteolytic activity, potentially enhancing AR signaling and contributing to aggressive tumor behavior. However, data on this variant in North African populations remain sparse.

A case-control study was conducted including 50 Moroccan men diagnosed with prostate cancer (PCa) and 50 matched controls. Genotyping of rs12329760 was performed using TaqMan allelic discrimination assays. Genotype and allele distributions were analyzed and correlated with clinicopathological factors, including serum PSA levels, Gleason score, family history, smoking status, and other demographic or clinical variables.

The CT (44% vs. 26%, P = 0.016) and TT (20% vs. 8%, P = 0.031) genotypes, as well as the T allele (43% vs. 21%, P = 0.002), were significantly more frequent in PCa patients than controls and were associated with increased disease risk. Carriers of the CT + TT genotypes exhibited significantly higher PSA levels (≥ 10 ng/mL, P = 0.004), Gleason scores (≥ 7, P = 0.018).Significant associations were also observed with positive family history (P < 0.001) and smoking (P < 0.001). No associations were found with age at diagnosis, T-stage.

The TMPRSS2 rs12329760 T allele is associated with elevated prostate cancer risk and more severe clinicopathological features in Moroccan men. These findings highlight the potential prognostic relevance of the V160M variant and emphasize the need for further cellular and molecular studies to elucidate its functional role in AR signaling, TMPRSS2-ERG fusion biology, and ERG-related tumor aggressiveness. Such insights may contribute to the development of risk-stratified PCa management and tailored active surveillance strategies.