CAJ | 학술논문

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2 ml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％ CI)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％ CI: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％ CI: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.
목적 탐토배양화매2(COX2)계동자구-1195G＞A유전변이여폐암유전역감성적관계이급여흡연적교호작용.방법 이2000년1월지2008년12월재중국의학과학원종류의원취진적956례폐암환자작위병례조；건강대조래자동기북경시건강체검개체,이무종류병사화체정자작위대조조,공994명.연구대상균위한족,무년령、성별한제.대조조여병례조상필배.경지정동의,매명연구대상균채집2 ml외주혈,이PCR-한제성편단장도다태성방법대연구대상진행기인분형,병차조사료대상적흡연정황.이logistic회귀법계산COX2-1195G＞A변이각기인형영향폐암발병풍험적OR치급95％ CI.결과 대조조、병례조기인분형위COX2-1195AA자분별점24.9％ (247/994)、28.3％ (271/956).여-1195GG기인형휴대자상비,-1195AA기인형휴대자폐암적발병풍험증가1.36배(95％ CI:1.03～ 1.79).이흡연진행분층분석,재흡연인군중,휴대COX2-1195AA기인형자,폐암적발병풍험명현증고,기OR(95％ CI)위1.56(1.08 ～2.25)；재비흡연조,미발현폐암발병풍험재불동기인형지간적차이(OR=1.17;95％ CI:0.77 ～ 1.61).재중도흡연자(＞20포/년)중,-1195AA화-1195AG기인형휴대자발생폐암풍험분별시-1195GG휴대자적1.85배(95％ CI:1.16 ～2.95)화1.62배(95％CI:1.08 ～2.43)；재경도흡연자(≤20포/년)중,-1195AG화AA기인형휴대자발생폐암풍험적OR(95％ CI)분별위0.78(0.47 ～ 1.30)화1.08(0.60～1.94).결론 COX2계동자구유전변이대폐암발병풍험적상관성화배경인소밀절상관.
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 frequencymatched controls were randomly selected 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％ CI 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-1195AA genotype carriers (OR =1.36,95％ CI:1.03-1.79),compared with-1195GG 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％ CI) 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:0.77-1.61).Among heavy smokers (pack-year ＞20),-1195AA and-1195AG 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-1195AA genotype carriers were 0.78 (0.47-1.30) and 1.08 (0.60-1.94),respectively.Conclusion Genetic polymorphism in the promoter of COX2 gene interacting with smoking factor plays an important role in the development of lung cancer.