Potentially functional polymorphisms of EXO1 and risk of lung cancer in a Chinese population: A case-control analysis

SummaryExonuclease 1 (EXO1) is an important nucleases involved in mismatch repair system that contributes to maintain genomic stability, to modulate DNA recombination, and to mediate cell cycle arrest. Potentially functional polymorphisms in EXO1 may alter cancer risks by influencing the repair activity of EXO1. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) in EXO1 were associated with risk of lung cancer. To test this hypothesis, we genotyped five common SNPs (rs1776177A/G, rs1047840G/A (Glu589Lys), rs1776148G/A (Gly670Glu), rs9350C/T (Leu757Pro) and rs851797T/C) that tag eight SNPs located at exon regions of EXO1 by using the Illumina high-throughput genotyping platform in 500 incident lung cancer cases and 517 cancer-free controls in a Chinese population. Significant differences of allele and genotype distributions were observed in Glu589Lys (rs1047840) of EXO1 between the cases and controls (P = 0.028 and 0.025 for allele and genotype distributions, respectively). Logistic regression analyses revealed that individuals carrying the variant 589Lys allele (589Glu/Lys or 589Lys/Lys) had a significantly increased risk of lung cancer [adjusted odds ratio (OR) = 1.41, 95% confidential interval (CI) = 1.09–1.84] compared with those who carried the wild-type homozygote (589Glu/Glu). Furthermore, we found that haplotype AAGTT was more frequent in cases than in controls (P < 0.001 for both two-sided χ2-test and 1000 times permutation tests). These results suggest that the EXO1 Glu589Lys polymorphism and its surrounding regions might be genetic susceptibility markers for lung cancer in this study population.