DNA双链断裂修复基因NBS1多态性与肺癌易感性的关联研究

Study on the association between DNA double-strand break repair gene NBS1 polymorphisms and susceptibility on lung cancer

目的探讨DNA双链断裂修复基因NBSI多态性与肺癌遗传易感性的关系。方法采用病例对照设计，应用PCR—RFLP技术检测575例患者和575名对照的NBS1基因多态。结果对照组和病例组NBSlrsl805794的C／C、C／G、G／G基因型频率分别为25．9％、51．8％、22．3％和20．5％、52．3％、27．1％，两组分布差异有统计学意义（χ^2=6．38，P=0．04），携带C／G＋G／G基因型个体患肺癌的风险是携带C／C基因型者的1．46倍（OR=1．46，95％CI：1．09～1．97）。对照组和病例组NBSlrs2735383的G／G、G／C、C／C基因型频率分别为37．9％、47．0％、15．1％和35．5％、48．5％、16．0％，两组分布差异无统计学意义（χ^2=0．75，P=0．69）。携带Hap4-GC单体型或Hap4／Hap2单体型对者患肺癌的风险增加，OR值分别为1．70（95％CI：1．24～2．31）和1．75（95％CI：1．11～2．76），NBSl基因多态与吸烟有联合作用（P〈0．05）。结论NBSlrsl805794G／G基因型可能是肺癌的易感基因型，rsl805794和rs2735383位点构建的Hap4-GC单体型及Hap4／Hap2单体型对可能是肺癌的易感单体型和单体型对。

Objective To study the association between DNA double-strand break repair gene NBS1 （nijmegen breakage syndrome gene） polymorphisms and the susceptibility to lung cancer. Methods A case-control study design was applied. PCR-RFLP was used to identify NBS1 polymorphisms among 575 lung cancer cases and 575 controls. Results The frequencies of C/C, C/G and G/G genotypes at NBSI rs1805794 site were 25.9%, 51.8%, 22.3% among controls compared to 20.5%, 52.3%, 27.1% among cases. There was significant difference between controls and cases （χ^2= 6.38, P：0.04）. Individuals carrying C/G ＋ G/G genotypes had an increased risk for lung cancer （OR： 1.46, 95%CI： 1.09-1.97） compared to the C/C genotype. The frequencies of G/G, G/C and C/C genotypes at NBS1 rs2735383 site were 37.9%, 47.0%, 15.1% among controls compared to 35.5%, 48.5%, 16.0% among cases, with no significant difference between the two groups （χ^2=0.75, P= 0.69 ）. Individuals carr） ing Hap4-GC haplotype （OR= 1.70,95% CI： 1.24-2.31 ） and Hap4/Hap2 dihaplotype （OR=1.75,95% CI： 1. 11-2.76） had an increased risk on lung cancer. Joint associations of smoking and the NBSI polymorphism with the risk of lung cancer were observed （P〈0.05）. Conclusion The G/G genotype at NBS 1 rs 1805794 site and the Hap4-GC haplotype and Hap4/Hap2 dihaplotype from rs 1805794 and rs2735383 were both associated with lung cancer.