中文摘要：

目的探讨肿瘤坏死因子-β（TNF—β）252A／G遗传变异与非小细胞肺癌（NSCLC）遗传易感性的关系。方法以2000年1月至2008年12月在中国医学科学院肿瘤医院就诊的956例NSCLC病例作为病例组；以来自同期北京市健康体检个体，无肿瘤病史和体征者作为对照组，共994名。研究对象均为汉族，对照组与病例组相匹配。经知情同意，每名研究对象均采集3ml外周血，以PCR．限制性片段长度多态性方法对研究对象进行基因分型，并且调查了对象的吸烟情况。以logistic回归法计算TNF—β252A／G变异各基因型影响NSCLC发病风险的0R及95％CI值。结果在对照组中，TNF-β252AA、AG和GG基因型分别占30．9％（307／994）、47．4％（471／994）和21．7％（216／994）；在病例组中，分别占35．7％（341／956）、48．1％（460／956）和16．2％（155／956）。logistic回归分析结果显示，与TNF-β252AA基因型携带者相比，GG基因型携带者具有较低的NSCLC发病风险，其OR（95％CI）值为0．64（0．49～0．83）。以携带AA基因型的非吸烟者作为参照，携带AA基因型的吸烟者发生NSCLC风险的OR（95％CI）值为2．88（1．91—2．24），高于GG基因型吸烟者发生NSCLC的风险（OR=1．54；95％CI：1．00—2．39）。进一步以累计吸烟量分层，携带AA基因型的重度吸烟者（〉20包／年）发生NSCLC的OR（95％CI）值为4．62（2．88—7．41），高于携带GG基因型的重度吸烟者（OR=2．24，95％CI：1．33～3．74）。结论TNF-β遗传变异对NSCLC发病风险有影响并与吸烟情况相关。

英文摘要：

Objective To investigate the association of TNF-β 252A 〉 G variant with the risk of non-small cell lung cancer （ NSCLC ）. Methods Total 956 patients with NSCLC were recruited between January 2000 and December 2008 at Cancer Hospital, Chinese Academy of Medical Science as the case group, and 994 frequency-matched controls were randomly selected from a pool of cancer-free subjects recruited from a nutritional group. All the participants were unrelated Han Chinese. There were no age, gender restrictions. Smoking status of the subjects was surveyed. Informed consent was obtained and 3 ml peripheral blood was collected from each subject. All samples were genotyped by polymerase chain reaction- restriction fragment length polymorphism method （PCR-RFLP）. The OR and 95% CI were estimated by logistic regression to evaluate the relationship between TNF-β 252 A/G variant and the risk of lung cancer. Results The frequencies of TNF-β 252 AA, AG and GG genotype were 30. 9% （307/994）, 47.4% （471/994）and 21.7% （216/994） in lung cancer cases and 35.7% （341/956） ,48. 1% （460/956） and 16. 2% （155/956） in controls. Logistic regression analysis revealed that TNF-β 252 GG genotype contributed to a decreased risk of developing NSCLC （ OR =0. 64, 95% CI： 0. 49 -0. 83） compared with AA genotype. When stratified by smoking status, the individuals with 252 GG genotype had a significant increased risk of NSCLC （OR = 1.54, 95% CI： 1.00- 2. 39 ） among smokers; which was less than those with AA genotyoe among smokers （ OR = 2. 88, 95% CI： 1.91 - 2. 24）. When further stratified by smoking index, individuals with 252 GG genotype had a significant decreased risk of NSCLC among heavy smokers with OR （95% C1） of 2.24 （ 1.33 -3.74）, which was less than those with AA genotype （ OR = 4. 62, 95% CI：2. 88 - 7.41 ）. Conclusion TNF-β genetic variant may interact with environment factor to contribute to the susceptibility to NSCLC.