中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2012年
1期
23-27
,共5页
陈春梅%金永堂%徐鹤云%张晨烨%张虎%张伟民%谭聪%孙肖瑜
陳春梅%金永堂%徐鶴雲%張晨燁%張虎%張偉民%譚聰%孫肖瑜
진춘매%금영당%서학운%장신엽%장호%장위민%담총%손초유
细胞色素氧化酶P4501A1基因%谷胱甘肽硫转移酶基因%基因多态性%BPDE-DNA加合物%肺癌%吸烟
細胞色素氧化酶P4501A1基因%穀胱甘肽硫轉移酶基因%基因多態性%BPDE-DNA加閤物%肺癌%吸煙
세포색소양화매P4501A1기인%곡광감태류전이매기인%기인다태성%BPDE-DNA가합물%폐암%흡연
CYP1A1 gene%GSTM1 gene%Genetic polymorphisms%BPDE-DNA adducts%Lung cancer%Smoking
目的 分析代谢酶基因细胞色素氧化酶P450(cytochrome P450,CYP450)1A1与谷胱苷肽硫转移酶M1(glutathione S-transferase μ1,GSTM1)的多态性和二羟环氧苯并芘(benzo A-pyrene-diolepoxide,BPDE)-DNA加合物之间的关系,并探讨其对肺癌发病的影响.方法 用病例-对照方法收集200例原发性肺癌患者的流行病学调查资料及外周血样本,采用限制性片段长度多态性-PCR法检测血中CYP1A1、GSTM1基因多态性,应用竞争性酶联免疫吸附法检测BPDE-DNA加合物浓度.结果 CYP1A1变异型吸烟者、GSTM1缺失型吸烟者患肺癌风险升高,OR值分别为2.406(1. 321~4. 382)和2.755(1.470~5.163).肺癌患者BPDE-DNA加合物浓度高于对照人群,且肺癌吸烟者加合物浓度明显高于肺癌不吸烟者(P=0.0252);GSTM1缺失型个体DNA加合物水平高于5.0加合物/108核苷酸时,患肺癌的风险升高(OR=1.988,95% CI:1.011~3.912);CYP1A1变异型吸烟者形成高水平DNA加合物的风险明显高于CYP1A1野生型不吸烟者(P=0.0459); GSTM1缺失型吸烟者形成高水平DNA加合物的风险高于GSTM1功能型不吸烟者(OR=2.432,95% CI:1.072~4.517).结论 GSTM1缺失型个体DNA加合物水平高更容易增加肺癌危险性;CYP1A1变异型吸烟者、GSTM1缺失型吸烟者更容易形成高水平的DNA加合物,对肺癌的发生可能有重要影响.
目的 分析代謝酶基因細胞色素氧化酶P450(cytochrome P450,CYP450)1A1與穀胱苷肽硫轉移酶M1(glutathione S-transferase μ1,GSTM1)的多態性和二羥環氧苯併芘(benzo A-pyrene-diolepoxide,BPDE)-DNA加閤物之間的關繫,併探討其對肺癌髮病的影響.方法 用病例-對照方法收集200例原髮性肺癌患者的流行病學調查資料及外週血樣本,採用限製性片段長度多態性-PCR法檢測血中CYP1A1、GSTM1基因多態性,應用競爭性酶聯免疫吸附法檢測BPDE-DNA加閤物濃度.結果 CYP1A1變異型吸煙者、GSTM1缺失型吸煙者患肺癌風險升高,OR值分彆為2.406(1. 321~4. 382)和2.755(1.470~5.163).肺癌患者BPDE-DNA加閤物濃度高于對照人群,且肺癌吸煙者加閤物濃度明顯高于肺癌不吸煙者(P=0.0252);GSTM1缺失型箇體DNA加閤物水平高于5.0加閤物/108覈苷痠時,患肺癌的風險升高(OR=1.988,95% CI:1.011~3.912);CYP1A1變異型吸煙者形成高水平DNA加閤物的風險明顯高于CYP1A1野生型不吸煙者(P=0.0459); GSTM1缺失型吸煙者形成高水平DNA加閤物的風險高于GSTM1功能型不吸煙者(OR=2.432,95% CI:1.072~4.517).結論 GSTM1缺失型箇體DNA加閤物水平高更容易增加肺癌危險性;CYP1A1變異型吸煙者、GSTM1缺失型吸煙者更容易形成高水平的DNA加閤物,對肺癌的髮生可能有重要影響.
목적 분석대사매기인세포색소양화매P450(cytochrome P450,CYP450)1A1여곡광감태류전이매M1(glutathione S-transferase μ1,GSTM1)적다태성화이간배양분병비(benzo A-pyrene-diolepoxide,BPDE)-DNA가합물지간적관계,병탐토기대폐암발병적영향.방법 용병례-대조방법수집200례원발성폐암환자적류행병학조사자료급외주혈양본,채용한제성편단장도다태성-PCR법검측혈중CYP1A1、GSTM1기인다태성,응용경쟁성매련면역흡부법검측BPDE-DNA가합물농도.결과 CYP1A1변이형흡연자、GSTM1결실형흡연자환폐암풍험승고,OR치분별위2.406(1. 321~4. 382)화2.755(1.470~5.163).폐암환자BPDE-DNA가합물농도고우대조인군,차폐암흡연자가합물농도명현고우폐암불흡연자(P=0.0252);GSTM1결실형개체DNA가합물수평고우5.0가합물/108핵감산시,환폐암적풍험승고(OR=1.988,95% CI:1.011~3.912);CYP1A1변이형흡연자형성고수평DNA가합물적풍험명현고우CYP1A1야생형불흡연자(P=0.0459); GSTM1결실형흡연자형성고수평DNA가합물적풍험고우GSTM1공능형불흡연자(OR=2.432,95% CI:1.072~4.517).결론 GSTM1결실형개체DNA가합물수평고경용역증가폐암위험성;CYP1A1변이형흡연자、GSTM1결실형흡연자경용역형성고수평적DNA가합물,대폐암적발생가능유중요영향.
Objective To investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis.Methods The case control study has included 200 cases of lung cancer and 200 controls.DNA was extracted from blood samples of all subjects.The genotype of both CYP1A1 and GSTM1 were detected with PCR-based restriction fragment length polymorphisms (PCRRELP).BPDE-DNA adducts were detected with competitive ELISA.Results CYP1A1 mutant genotype and GSTM1 null genotype with smoke has increased the risk of lung cancer,with OR being 2.406 (1.321-4.382),2.755(1.470-5.163),respectively.The level of BPDE-DNA adducts in patients was greater than control,and the adduct level in ever smokers was higher than never smokers,the difference was statistically significant (P=0.0252).GSTM1 null genotype individuals with BPDE-DNA level higher than 5 adducts/108 nucleotide have increased risk of lung cancer (OR=1.988,95%CI:1.011-3.912).Compared with never smokers with CYP1A1 wild genotype,smokers with CYP1A1 mutation genotype had an increased risk of forming a higher level of DNA adducts (P=0.0459).Smokers with GSTM1 null genotype formed more DNA adducts compared with never smokers with GSTM1 functional genotype (OR =2.432,95% CI:1.072-4.517).Conclusion GSTM1 null genotype with higher level DNA adducts may increase the risk of lung cancer. DNA adducts form easier in smokers with CYP1A1 mutation genotype and GSTM1 null genotype,which in turn may influence lung tumorigenesis.