[Combined effects of genetic polymorphisms in cytochrome P450s and GSTM1 on lung cancer susceptibility].
OBJECTIVE
To investigate the relationship between the gene polymorphism of metabolizing enzymes and the genetic susceptibility to lung cancer as well as to study the synergistic effects between smoking and the genes.


METHODS
Peripheral blood samples were collected from 279 patients with primary lung cancer and 684 age-, nationality-, and native place-matched controls, including patients with benign diseases and healthy volunteers. PCR-RELP was used to detect the distribution of CYP1A1, 2D6, 2E1, and GSTM1 genotypes. The correlation of these genes with the sensibility to lung cancer was analyzed.


RESULTS
The CYP1A1 variant allele frequency of the lung cancer group was 67.4%, significantly higher than that of the control group (55.7%, P = 0.001). GSTM1-null genotype was found to be associated with lung cancer (OR = 1.58, P = 0.002). The risk of lung cancer in the individuals carrying GSTM1-null genotype and CYP1A1 (w/m, m/m) genotype was 2.75 times that of the individuals not carrying these genotypes (P < 0.01). There were no significant differences in the frequencies of CYP2D6 and CYP2E1 genotypes between these two groups. In the heavy smokers GSTM1-null, CYP1A1, CYP2D6, and CYP2E1 genotypes increased the risk of lung cancer by 5.71 - 11.67 times (P = 0.000).


CONCLUSIONS
The individuals who carry GSTM1-null genotype and CYP1A1 (m) genotype have an increase risk of lung cancer. The combined effect of I phase metabolizing enzymes and II phase metabolizing enzymes is observed. In heavy smokers the polymorphism of GSTM1 and CYPs affects the susceptibility to lung cancer.
Gu
Yan-Fei
YF
Department of Oncology, Beijing Chest Hospital, Beijing 101149, China.
Zhang
Zong-De
ZD
Zhang
Shu-Cai
SC
Zheng
Su-Hua
SH
Jia
Hong-Yan
HY
Gu
Shu-Xiang
SX
D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000209:etiology / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012907:Smoking / Q000009:adverse effects
D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase