环氧化酶2遗传变异与吸烟交互作用影响肺癌易感性  

Cyclooxygenase 2 genetic variant interacting with tobacco smoking and the risk of lung cancer

作　　者：张志[1,2] 刘睿[1] 杨照环[1] 王光霞[1] 邵莎莎[1] 宋琴琴[1] 张雪梅[2] 

机构地区：[1]唐山市工人医院肿瘤放化疗科,063000 [2]河北联合大学生命科学学院

出　　处：《中华预防医学杂志》2013年第8期736-740,共5页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金（81101483）;河北省杰出青年科学基金（H2012401022）

摘　　要：目的探讨环氧化酶2（COX2）启动子区-1195G〉A遗传变异与肺癌遗传易感性的关系以及与吸烟的交互作用。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例肺癌患者作为病例组；健康对照来自同期北京市健康体检个体，以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，无年龄、性别限制。对照组与病例组相匹配。经知情同意，每名研究对象均采集2ml外周血，以PCR-限制性片断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COX2-1195G〉A变异各基因型影响肺癌发病风险的OR值及95％CI。结果对照组、病例组基因分型为COX2—1195AA者分别占24．9％（247／994）、28．3％（271／956）。与-1195GG基因型携带者相比，-1195AA基因型携带者肺癌的发病风险增加1．36倍（95％CI：1．03～1．79）。以吸烟进行分层分析，在吸烟人群中，携带COX2—1195AA基因型者，肺癌的发病风险明显增高，其OR（95％C1）为1．56（1．08～2．25）；在非吸烟组，未发现肺癌发病风险在不同基因型之间的差异（OR=1．17；95％C1：0．77～1．61）。在重度吸烟者（〉20包／年）中，-1195AA和-1195AG基因型携带者发生肺癌风险分别是-1195GG携带者的1．85倍（95％C1：1．16～2．95）和1．62倍（95％CI：1．08—2．43）；在轻度吸烟者（≤20包／年）中，-1195AG和AA基因型携带者发生肺癌风险的OR（95％CI）分别为0．78（0．47～1．30）和1．08（0．60～1．94）。结论COX2启动子区遗传变异对肺癌发病风险的相关性和环境因素密切相关。Objective To explore the association of - 1195G 〉 A genetic variant in the promoter region of cyclooxygenase 2 genetic （COX2） with the genetic susceptibility of lung cancer and its interaction with smoking. Methods Totally, 956 lung cancer patients 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 seleeted from a pool of cancer-free subjects recruited from a nutritional survey. All subjects were ethnic Han Chinese. There was no sex, age restrictions. Case group and control group were matched. Informed consent was obtained and 2 ml peripheral blood was collected from each subject. All samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism method, smoking status of the subjects was surveyed. While the OR and 95% C1 were estimated by logistic regression to evaluate the relation of COX2 - 1195G 〉 A variant and the risk of lung cancer. Results The genetic allele COX2 - 1195AA of control group and case group were 24. 9% （247/994） and 28.3% （271/ 956）. Case-control analysis showed an increased risk of developing lung cancer for - I195AA genotype carriers （OR = 1.36, 95% CI： 1.03 - 1.79）, compared with - l195GG carriers. When stratified by smoking status, the significant increased risk of lung cancer was found among smokers with COX2 - 1195AA genotype, with the OR （95% C1） was 1.56 （ 1.08 -2.25） ; while among non-smokers, difference of lung cancer risk was not found among different genotypes （ OR = 1.17 ; 95% CI： O. 77 - 1.61 ）. Among heavy smokers （pack-year 〉 20）, -l195AA and -l195AG genotype carriers have significant increased risk of lung cancer with 1.85 （ 1.16 -2. 95 ） and 1.62 （ 1.08 -2. 43 ） of OR （95 % CI）, respectively; among light smokers （ pack-year ≤ 20 ）, the OR （95% CI） of lung cancer risk in - 1195AG and - 1195 AA genotype caaiers were 0. 78 （ 0. 47 - 1.30 ） and 1.08 （ 0. 60 - 1

关 键 词：环氧化酶2 肺肿瘤 遗传变异 多态性 单核苷酸 

分 类 号：R734.2[医药卫生—肿瘤]