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

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南京医科大学学报(自然科学版) 2008年第10期 1368-1368页

作者： Jin, G. F. Wang, H. F. Hu, Z. B. Liu, H. L. Sun, W. W. Ma, H. X. Chen, D. Miao, R. F. Tian, T. Jin, L. Wei, Q. Y. Huang, W. Lu, D. R. Shen, H. B. Nanjing Med Univ, Canc Res Ctr, Dept Epidemiol & Biostat, Nanjing 210029, Peoples R China. Chinese Natl human Genome Ctr, Shanghai MOST Key Lab Hlth & Dis Genom, Dept Genet, Shanghai 201203, Peoples R China. Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.

Exonuctease 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 EX01. Therefore, we hypothesized that single nucteotide polymorphisms(SNPs) in EX01 were associated with risk of lung cancer. To test this hypothesis, we genotyped five common SNPs (rs1776177A/G, rs1047840G/A(Gtu589Lys), rs1776148G/A(Gly670Glu), rs9350C/T(Leu757Pro) and rs851797T/C) that tag eight SNPs located at exon regions of EX01 by using the ilumina high-throughput genotyping platform in 500 incident lung cancer cases and 517 cancerfree controls in a Chinese population. Significant differences of allele and genotype distributions were observed in Gtu589Lys (rs1047840) of EX01 between the cases and controls (P = 0.028 and 0.025 for allele and genotype distributions, respectively). Lo- gistic 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(Cl) = 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 ided chi(2)-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. (c)2007 Elsevier ireland Ltd. All rights reserved.

关键词： EXO1 MMR Polymorphisms lung cancer susceptibility molecular epidemiology nonpolyposis colorectal-cancer dna mismatch repair single nucleotide polymorphisms human exonuclease-i mutation avoidance gene recombination inactivation variants tobacco

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