DNA修复基因XRCC3多态性与肺癌易感性的关系

Relationship between polymorphisms of DNA repair gene XRCC3 and susceptibility to lung cancer

目的研究 DNA 修复基因 XRCC3多态性与肺癌易感性的关系。方法采用病例-对照研究,于2006年9月至2007年1月收集上海肺科医院原发性肺癌患者291例及同期住院的非肿瘤患者273例,应用 Taqman 探针结合实时荧光 PCR 方法分析病例组和对照组 XRCC3基因Thr241Met 的多态性分布,比较不同基因型与肺癌易感性的关系以及基因多态性与吸烟对肺癌的交互作用。对照组与病例组的比较用 X^2检验,以调整比值比及95%可信区间表示相对危险度,所有统计检验均为双侧概率检验,所有资料均用 SPSS 软件进行统计。结果与携带 XRCC3密码子241野生纯合基因型(Thr/Thr)且不吸烟者相比,携带同样基因型且吸烟者患肺癌的风险会增加,其调整比值比(OR 值)为2.47[95%可信区间(CI)为1.49～4.08,P<0.01];携带有杂合基因型(Thr/Met)且吸烟者患肺癌的风险也会增加,其调整 OR 值为2.28(95%CI 为1.21～6.60,P=0.017)。野生纯合基因型(Thr/Thr)且吸烟量少于30包年可能对肺腺癌有较弱的保护作用(OR=0.49,95%CI 为0.26～0.93,P=0.03)。携带有 XRCC3密码子241Met 等位基因且吸烟者患肺鳞癌的风险明显增加(调整 OR=9.69,95%CI 为3.27～28.72,P<0.01)。携带241Met 等位基因且吸烟剂量<30包年和≥30包年的患者患肺鳞癌的风险也不同,OR 值分别为8.00(95%CI 为1.97～32.52,P<0.01)和11.67(95%CI 为2.98～45.73,P<0.01)。结论 DNA 修复基因 XRCC3多态性可能对肺癌易感性产生影响,并可能与吸烟有一定的协同作用。

Objective To study the polymorphisms of DNA repair gene XRCC3 and the relationship between genetic variations and susceptibility to lung cancer. Methods A case-control study of 291 patients with lung cancer and 273 cancer-free subjects as a control group was conducted from September 2006 to January 2007 to detect XRCC3 polymorphisms at loci. Genotypes of XRCC3 were analyzed by real time PCR using Taqman probes. Results Compared with never smoking subjects with wild homozygous genotype （Thr/Thr）, smokers with the same genotytpe （Thr/Thr）had increased risk of lung cancer, adjusted odds ratio （OR） was 2. 467（95% CI： 1.49 -4. 08, P 〈 0. 001 ）. Smokers with the heterozygous genotype（ Thr/Met） also had increased risk of lung cancer, adjusted OR was 2. 283 （ 95% CI. 1.21 - 6. 60, P 〈 0. 05 ）. XRCC3 codon 241 homozygous genotype （Thr/Thr） and pack-years of smoking less than 30 had a weak protective effect on adenocarcinoma （ OR = 0. 49,95% CI：O. 26 -0.93, P 〈 0. 05）. Allel Met of XRCC3 codon 241 and smoking conferred an increased risk of squamous cell carcinoma （ OR = 9.69, 95% CI： 3.27 -28.72, P 〈0.01 ）. Those with allel Met of XRCC3 codon 241 and pack-years of smoking less than 30 or more than 30 had different risk of squamous cell carcinoma,the OR was 8. 00 （95% CI：I. 97 -32.52, P〈0.01）, and 11.67 （95% CI. 2.98 -45.73 , P〈0.01） respectively. Conclusion The results demonstrated that genetic polymorphism of XRCC3 DNA repair gene may contribute to the susceptibility to lung cancer and have svneraistic effect with smokinz.