A meta-analysis and expression profiling of DNA repair gene polymorphisms in leukemia

Genetic susceptibility is believed to contribute to leukemia development. This study aimed to systematically evaluate the association between DNA repair gene polymorphisms, particularly xeroderma pigmentosum (XP) and excision repair cross-complementing (XRCC) genes, and leukemia risk.

A comprehensive search of PubMed, Web of Science, Scopus, and Cochrane Library was conducted until December 3, 2025, concerning the association between DNA repair gene polymorphisms and leukemia risk. Gene expressions were performed in Leukemia DB, GEPIA2, and BloodSpot datasets.

Fifty-four studies were included in the meta-analysis. No significant associations were observed for ERCC1 C118T or XPD Asp312Asn across genetic models, whereas ERCC1 8092C>A showed significant associations in homozygous and dominant models. The XPD Lys751Gln polymorphism demonstrated significant associations across all models. Significant associations were identified for XPC Lys939Gln in allelic, homozygous, and recessive models and for XPF Arg415Gln in the heterozygous model. XPG 3507G>C showed no significant association. XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Met polymorphisms were significantly associated with leukemia risk, while XRCC1 Arg280His was not. Gene expression analyses revealed subtype-specific alterations in DNA repair genes across leukemia datasets.

Several DNA repair polymorphisms, including XPD Lys751Gln, XPC Lys939Gln, XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 Thr241Met, are associated with increased leukemia susceptibility. Differential expression patterns of DNA repair genes across leukemia subtypes suggest functional heterogeneity and highlight their potential relevance in risk stratification and biomarker development.