Interaction between genetic polymorphisms of XRCC1 gene and cigarette smoke exposure as risk for acute lymphoblastic leukemia in Thai children

Abstract

Polymorphisms of DNA repair genes can alter protein structure and may impair DNA repair capacity. Defects in repairing damaged DNA lead to genetic instability and carcinogenesis. This study was performed to evaluate the effect of the polymorphisms of DNA repair genes on risk of childhood acute lymphoblastic leukemia (ALL), We studied polymorphisms of X-ray repair cross-complimenting group 1 (XRCC1) codon 194 (Arg to Trp), 280 (Arg to His) and 399 (Arg to Gln) and interaction between cigarette smoke and leukemia in 139 children with ALL compared to age and sex matched control. The XRCC1 399 and 194 was associated with a significantly increased risk of ALL whereby codon 399 polymorphism (Odds ratio (OR), A/G OR=3.17, 95% confidence interval (95% CI) =1.42-7.06 and A/A OR=2.94, 95% CI =1.73-5.00) had an increased risk of ALL higher than codon 194 (T/C OR=2.00, 95% CI =1.14-3.53). The haplotype (codon 194-280-399) that were associated with an increased risk of childhood ALL were type D (C-G-A, OR=4.38, 95% CI=2.64-7.33), type E (T-G-A, OR=4.19, 95% CI=1.55-2.44), type F(C-A-G, OR=3.03, 95% CI=1.69-5.48) and type H (T-G-G, OR=2.55, 95% CI=1.42-4.60). In contrast, the distribution of the allele and genotype frequency of XRCC1 codon 280 was not associated with increased risk of ALL. For ALL cases and controls, no significant difference of active and passive exposure was observed between ALL cases and controls.