Association of XPD Gene Polymorphisms with Cutaneous Melanoma Risk: A Meta-Analysis and Trial Sequence Evaluation

BACKGROUND: Conflicting results have emerged regarding the relationship between XPD polymorphisms and cutaneous melanoma (CM) susceptibility. This meta-analysis aims to clarify this association. METHODS: A thorough literature search was performed in PubMed, Scopus, Web of Science, and CNKI databases up to September 1, 2023. RESULTS: The analysis included 27 case-control studies comprising 11,293 cases and 14,437 controls. Thirteen studies focused on the Lys751Gln polymorphism (3,319 cases and 6,845 controls), ten on the Asp312Asn polymorphism (4,150 cases and 5,527 controls), and four on the Arg156Arg polymorphism (1,824 cases and 2,065 controls). The pooled analyses revealed no significant association between the XPD Lys751Gln and Asp312Asn polymorphisms and CM. However, the XPD Arg156Arg polymorphism showed a significant association with the AA genotype (OR = 1.191, p = 0.034), indicating an increased risk, particularly among Caucasians (AA vs. AC+CC OR = 1.203, p = 0.033). CONCLUSIONS: The XPD Arg156Arg polymorphism may increase CM risk, especially in Caucasians, while the Lys751Gln and Asp312Asn polymorphisms do not show a consistent association with CM risk. Further research in larger and more diverse ethnic populations is needed to confirm these findings.