Xing De-yin, Qi Jun, Tan Wen, Miao Xiao-ping, Liang Gang, Yu Chun-yuan, Lu Wen-fu, Zhou Chuan-nong, Wu Min, Lin Dong-xin
Department of Etiology Carcinogenesis, Cancer Institute Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003 Feb;20(1):35-8.
XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study.
Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression.
Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0.55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smoking>or=29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found.
The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.
已证实XPD基因在Asp312Asn和Lys751Gln位点的多态性可调节DNA修复能力。因此,作者通过一项基于医院的病例对照研究,评估了这些XPD基因多态性与中国人群肺癌和食管癌易感性之间的关系。
采用聚合酶链反应-限制性片段长度多态性方法,对383名健康对照者、351例肺癌患者和325例食管鳞状细胞癌(SCC)患者进行基因分型。使用多因素logistic回归计算调整后的比值比(OR)和95%可信区间(CI)。
与Asp/Asp基因型个体相比,携带至少一个312Asn变异等位基因(Asp/Asn和Asn/Asn基因型)的个体患肺鳞状细胞癌的风险增加(OR 1.80;95%CI:1.10-2.93;经年龄、性别和吸烟因素调整),但在肺腺癌患者中未观察到这种风险增加(调整后的OR:1.07;95%CI:0.55-2.08)。此外,分层分析表明,吸烟与XPD基因312Asn和751Gln变异等位基因之间在肺鳞状细胞癌风险上存在相乘交互作用。吸烟≥29包/年时,XPD基因312Asn和751Gln变异等位基因患肺鳞状细胞癌的OR分别为12.44(95%CI:4.97-31.17)和10.74(95%CI:4.51-25.57)。未发现Asp312Asn或Lys751Gln多态性与食管癌风险之间存在显著关联。
上述研究结果表明,在该中国人群中,XPD基因座的Asp312Asn和Lys751Gln多态性与肺鳞状细胞癌风险相关,但与肺腺癌或食管鳞状细胞癌风险无关。