Abstract
BACKGROUND: While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive. AIMS: This meta-analysis was thus developed with the goal of generating more precise estimates of the relationships between polymorphisms in four apoptosis-associated genes (NKX3-1, caspase-3, caspase-9, and BCL-2) and the risk of PCa. METHODS AND RESULTS: The PubMed, Web of Science, Google Scholar, Embase, Cochrane Library, and SinoMed (CNKI and Wanfang) databases were searched for relevant studies published through December 20, 2023, using the following keywords: "polymorphism" or "variant" and "carcinoma" or "cancer" or "tumor" and "NKX3-1," "CASP3" or "Caspase-3," "CASP9" or "Caspase-9," "BCL-2" or "B-cell lymphoma" and "prostate cancer" or "PCa" or "prostate adenocarcinoma." This approach led to the identification of 22 case-control studies related to the association between apoptosis-related gene polymorphisms and PCa susceptibility enrolling 9706 cases and 12 567 controls. Subsequent analyses revealed that the NKX3-1 rs2228013, CASP9 rs1052571, and CASP9 rs4645982 polymorphisms were associated with greater PCa risk, whereas the CASP3 rs4647603 polymorphism was associated with a risk reduction. CONCLUSION: These findings provide strong evidence for the potential contributions of polymorphisms in the apoptosis-related caspase-3, caspase-9, and NKX3-1 genes in the onset and progression of PCa.