XRCC3遗传变异与喉癌和下咽癌发病风险相关研究

Association between genetic polymorphism in DNA repair genes XRCC3 and risks of laryngeal and hypopharyngeal carcinomas

目的研究 DNA 修复基因 XRCC3 Thr 241 Met 遗传变异与喉癌和下咽癌风险的关系。方法采用聚合酶链反应-限制性片段长度多态分析方法对175例喉癌及下咽癌患者和525名无肿瘤对照进行基因分型,采用多因素 Logistic 回归模型计算各基因型携带者喉癌和下咽癌的发病风险,以及与吸烟交互对喉癌下咽癌发病风险的影响。结果 XRCC3 241 Met 等位基因增加了喉癌、下咽癌发病风险,与 XRCC3 241 Thr/Thr 基因型携带者相比,至少携带一个241 Met 等位基因的个体罹患喉癌、下咽癌的比值比(odds ratio,OR)为2.26,95%可信区间(confidence interval,CI)为1.33～3.82。分别分析 XRCC3多态与喉癌及下咽癌发病风险关系发现,XRCC3 241 Met 等位基因均增加喉癌与下咽癌的发生风险,与 XRCC3 241 Thr/Thr 基因型携带者相比,至少携带一个 XRCC3 241 Met 等位基因的个体发生喉癌和下咽癌风险的 OR 值(95%CI)分别为2.27(1.26～4.09)和2.99(1.27～7.04)。基因吸烟交互作用分析结果显示,重度吸烟和 XRCC3 Thr 241 Met 多态存在相乘交互作用,显著增加喉癌、下咽癌发病风险。至少携带一个 XRCC3 241 Met 等位基因的重度吸烟个体发生喉癌、下咽癌的 OR 值(95%CI)为19.09(7.38～49.40),大于至少携带一个 XRCC3 241 Met 等位基因的不吸烟个体(OR,0.91;95%CI,0.20～4.21)及重度吸烟但携带 XRCC3 241 Thr/Thr 基因型个体(OR,4.13;95%CI,2.38～7.17)的 OR 乘积。结论 XRCC3 Thr 241 Met 单核苷酸多态是喉癌、下咽癌的遗传易感因素。

Objective To study the association between polymorphism of DNA repair gene XRCC3 Thr 241 Met and the risks of developing laryngeal and hypopharyngeal carcinomas. Methods One hundred and seventy five patients with laryngeal or hypopharyngeal carcinoma and 525 cancer-free controls were genotyped for the polymorphism by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） . The odds ratios （ORs） and 95% confidence intervals （CIs） were calculated using unconditional logistic regression model. Results The XRCC3 241 Met allele increased the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. Comparing with subjects having the XRCC3 241 Thr/Thr genotype, the subjects at least having one XRCC3 241 Met allele had OR of 2.26 （95% CI 1.33 - 3.82）. Respectively analyzing the risks of laryngeal carcinoma and hypopharyngeal carcinoma, The allele XRCC3 241 Met increased the risks of developing both laryngeal and hypopharyngeal carcinoma. Comparing with the subjects having the XRCC3 241 Thr/Thr genotype, the subjects with laryngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2. 27 （95% CI 1.26 -4.09） ; the subjects with hypopharyngeal carcinoma at least having one XRCC3 241 Met genotype had OR of 2. 99 （95% CI 1.27 - 7.04）. Smoking may increase the risk of developing laryngeal carcinoma and hypopharyngeal carcinoma. The interaction of smoking and XRCC3 Thr241 Met increased risk of laryngeal carcinoma and hypopharyngeal carcinoma in a super-multiplicative manner. The subjects with heavy smoking and at least having one XRCC3 241 Met allele had OR of 19.09 （95% CI 7. 38 -49. 40） comparing with those having the XRCC3 241 Thr/ Thr genotype and no smoking, which was greater than the multiplication of ORs both of subjects at least having one 241 Met allele meanwhile without smoking （OR, 0. 91 ;95% CI,0. 20 -4. 21 ）and of subjects having XRCC3 241 Thr/Thr genotype meanwhile with smoking （ OR, 4. 13 ; 95% CI, 2.38 - 7. 17 ）. Conclusions XRCC3 Thr 241 Met plays an important role in the development of laryngeal and hypopharyngeal carcinoma.