摘要
背景与目的:肺癌是由环境和遗传两大类因素联合作用导致的复杂疾病,其中DNA损伤是肺癌遗传病因中的重要组分。作为参与多条DNA损伤修复通路的关键因子,DNA连接酶与肺癌发生可能存在联系。本文旨在研究DNA连接酶基因LIG1外显子6多态性与肺癌易感性的关系,并探索其与吸烟可能的交互作用。方法:采用病例-对照研究,收集原发性肺癌患者396例为病例组,同时随机抽取465名当地健康居民作为对照组,进行流行病学调查。运用PCR-RFLP方法分析LIG1基因外显子6的多态性。应用Logistic回归模型分析该位点多态性与肺癌易感性的关系。结果:突变等位基因C在病例组和对照组中的频率分别为28.41%和26.02%,两组间差异无显著性(P=0.2667)。相对于野生型A/A,携带A/C基因型者患肺癌的危险度为1.20(95%CI:0.90~1.62);而患肺腺癌和肺鳞癌的危险度分别达到1.45(95%CI:0.93~2.26)和1.57(95%CI:0.93~2.65)。在肺腺癌的发病中,LIG1多态的突变基因型与吸烟之间存在临界显著的负交互作用(OR=0.44,95%CI=0.18~1.06)。结论:DNA连接酶基因LIG1外显子6多态性可能与肺腺癌和肺鳞癌的易感性有关。
Background and purpose: Lung cancer is a complicated disease that could be induced by both environmental and genetic factors. DNA damage is one of the most critical component in the genetic etiology of lung cancer. DNA ligase, which is included in several paths of DNA repaire might associated to the development of lung cancer. Consequently, we conducted this study to explore the relationship between the polymorphisms of DNA ligase Ⅰ gene LIGI exon-6 and the susceptibility to lung cancer and evaluate the possible interaction between LIGI and tobacco smoking for with the risk of lung cancer. Methods: A case-control study including 396 newly diagnosed lung cancer cases and 465 healthy resident controls was conducted. We employed the PCR-based restriction fragment length polymorphism (RLFP) techniques to analyze the LIGI polymorphism at exon-6. The data were analyzed using logistic regression model. Results: The frequency of mutational allele C was 28.41% in the lung cancer cases and 26.02% in healthy controls, respectively. No statistically significant difference was observed (P=0.2667). Compared to A/A carrier, the subjects carrying A/C genotype were observed to have borderline higher risk of all types of lung cancer (OR=I.20, 95%CI: 0.90-1.62), adenocarcinoma (OR=1.45, 95% CI: 0.93-2.26), and squamous cell carcinoma (OR=1.57, 95% CI: 0.93-2.65). Moreover, a borderline significant negative interaction between mutative genotype of LIG 1 polymorphism and smoking was observed in the occurrence of lung adenocarcinoma (OR=0.44, 95% CI=0. 18- 1.06). Conclusions: The results suggested that genetic polymorphism of DNA ligase l gene LIG1 exon-6 might be associated with the susceptibility to lung adenocarcinoma and squamous cell carcinoma.
出处
《中国癌症杂志》
CAS
CSCD
2008年第7期481-486,共6页
China Oncology
基金
国家自然科学青年基金项目(项目编号30500417)