DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute lymphoblastic leukemia

Polymorphisms have been identified in several DNA repair genes. These polymorphisms may effect DNA repair capacity and modulate cancer susceptibility. In this study, we aimed to determine the four polymorphisms in two DNA repair genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with childhood acute lymphoblastic leukemia (ALL), and evaluate their association with childhood ALL development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1 Arg194Trp, and XRCC1 Arg399Gln polymorphisms in 70 patients with childhood ALL and in 75 disease-free controls, who were of a similar age. No significant differences were observed among the study groups with regard to the XPD codon 312, XPD codon 751, XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However, the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with increased risk for ALL in females (OR = 5.47; 95% CI = 1.49–20.10; p = 0.008). This finding indicates that females carrying XRCC1 194Trp allele are at increased risk of developing childhood ALL. These results suggest that the risk of childhood ALL may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing childhood ALL, and also should be lead to improved treatment of ALL.