Association of XRCC6 -61 C > G and XRCC7 6721G > T polymorphisms with susceptibility to pediatric acute lymphoblastic leukemia.

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children. The XRCC6 and XRCC7 genes play a key role in the nonhomologous end-joining (NHEJ) repair process and may influence susceptibility to ALL. The aim of this study is to evaluate the polymorphisms XRCC6 -61 C > G (rs2267437) and XRCC7 6721G > T (rs7003908) in children with ALL.

Materials and methods: Genomic DNA was extracted from the buffy coat from whole blood samples of patients. Genotyping of XRCC6 -61 C > G and XRCC7 6721G > T polymorphisms was performed by PCR followed by restriction fragment length polymorphism (PCR-RFLP) using specific restriction enzymes (BanI and Pvu II).

Results: In this investigation significant associations were discovered between XRCC6 -61 C > G genotypes CC (P = 0.006) and CG (P = 0.01) with ALL patients. It is important to note that while the CC genotype association remained significant after Bonferroni correction (P < 0.01), the CG genotype association was nominal (P between 0.01 and 0.05) and should be interpreted with caution. XRCC7 6721G > T genotypes GT (P = 0.02) and TT (P = 0.05) were significantly associated with ALL in males and females, respectively. In ALL patients with B-Cell subtype, XRCC6 -61 C > G genotypes CC (P = 0.04), GC (P = 0.05), and C allele (P = 0.05) showed significant associations. XRCC7 6721G > T genotypes GT (P = 0.003) and TT (P = 0.05) were also significantly associated in B-Cell ALL. Significant associations were observed for XRCC6 -61 C > G genotype CC (P = 0.04) and C allele (P = 0.03) in ALL patients with favorable cytogenetic abnormalities.

Conclusions: In conclusion, our findings suggest that the XRCC6 -61 C > G and XRCC7 6721G > T polymorphisms may be associated with susceptibility to pediatric ALL, with potential lineage-specific and cytogenetic context-dependent effects. However, given the exploratory nature of our subgroup analyses and the statistical limitations, these results should be interpreted cautiously. Large-scale, multi-center studies with functional validation are needed to confirm these associations and elucidate the underlying mechanisms.