Association of XPD Genetic Variations with Prostate Cancer Risk: Consolidated Results from 31 case-control studies

Background This study aims to perform a comprehensive meta-analysis of existing literature to elucidate the associations between genetic variations in the XPD gene and the risk of prostate cancer development. Methods A systematic search of multiple databases, including PubMed, Scopus, EMBASE, and CNKI, was executed up until January 1, 2025, to collect pertinent information. The search utilized relevant keywords and MeSH terms pertaining to prostate cancer and genetic factors. Inclusion criteria were established for original case-control, longitudinal, or cohort studies. Associations were assessed as odds ratios (ORs) with 95% confidence intervals (CIs) employing Comprehensive Meta-Analysis software. Results This review included 31 case-control studies featuring 11,632 prostate cancer cases and 14,661 healthy controls. The polymorphism rs13181 (Lys751Gln) was studied in 16 studies with 5,295 cases and 7,199 controls, rs1799793 (Asp312Asn) in 10 studies with 3,316 cases and 4,310 controls, and rs238406 (Arg156Arg) in five studies with 3,021 cases and 3,152 controls. Pooled analyses indicated a significant association between the XPD rs13181 polymorphism and prostate cancer risk across all genetic models assessed. However, both rs238406 and rs1799793 polymorphisms showed no overall association with prostate cancer risk. Subgroup analyses revealed a significant link between rs13181 and rs238406 polymorphisms and prostate cancer risk in Asian populations, with no such association found in Caucasian or African groups. Furthermore, rs1799793 did not show a significant association with prostate cancer when examined by ethnicity. Conclusions The analysis of polymorphisms XPD rs13181 and rs238406 shows that the rs13181 G allele is significantly associated with increased prostate cancer risk, particularly in the Asian population. The rs238406 polymorphism displays a marginal association in the overall population but significant risk among Asians. Conversely, the rs1799793 polymorphism does not show meaningful associations in any group. These findings indicate that genetic factors may influence prostate cancer risk, with varying associations across ethnicities.