[细胞色素P4501A1和谷胱甘肽S-转移酶M1基因多态性及苯并[a]芘二醇环氧化物-DNA加合物对肺癌的影响]

[Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer].

作者信息

Chen Chun-mei, Jin Yong-tang, Xu He-yun, Zhang Chen-ye, Zhang Hu, Zhang Wei-min, Tan Cong, Sun Xiao-yu

机构信息

Laboratory of Environment Epigenetics, Institute of Environmental Health, College of Public Health, Zhejiang University Medical School, Hangzhou, Zhejiang 310058, P. R. China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Feb;29(1):23-7. doi: 10.3760/cma.j.issn.1003-9406.2012.01.007.

DOI:10.3760/cma.j.issn.1003-9406.2012.01.007

PMID:22311486

Abstract

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 (PCR-RELP). 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/10(8) 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.

摘要

目的

探讨细胞色素P450 1A1（CYP1A1）和谷胱甘肽S-转移酶M1（GSTM1）基因多态性及苯并[a]芘二醇环氧化物（BPDE）-DNA加合物对肺癌发生的影响。

方法

病例对照研究纳入200例肺癌患者和200例对照。从所有受试者的血样中提取DNA。采用基于聚合酶链反应的限制性片段长度多态性（PCR-RELP）检测CYP1A1和GSTM1的基因型。采用竞争性酶联免疫吸附测定法检测BPDE-DNA加合物。

结果

携带CYP1A1突变基因型和GSTM1无效基因型且吸烟的人群患肺癌风险增加，比值比（OR）分别为2.406（1.321～4.382）、2.755（1.470～5.163）。患者的BPDE-DNA加合物水平高于对照，且曾经吸烟者的加合物水平高于从不吸烟者，差异有统计学意义（P = 0.0252）。BPDE-DNA水平高于5个加合物/10⁸核苷酸的GSTM1无效基因型个体患肺癌风险增加（OR = 1.988，95%可信区间：1.011～3.912）。与CYP1A1野生基因型的从不吸烟者相比，CYP1A1突变基因型的吸烟者形成更高水平DNA加合物的风险增加（P = 0.0459）。与GSTM1功能基因型的从不吸烟者相比，GSTM1无效基因型的吸烟者形成更多DNA加合物（OR = 2.432，95%可信区间：1.072～4.517）。