Genetic polymorphism of T6235C mutation in 3′ non-coding region of CYP1A1 and GSTM1 genes and lung cancer susceptibility in the Mongolian population / 西安交通大学学报·英文版

ABSTRACT

Objective: To estimate the relative risk for lung cancer associated with genetic polymorphism of T6235C mutation in 3′ non-coding region (MspI) of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1(GSTM1) in the Mongolian population in Inner Mongolian Region of China. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR methods were used to analyze blood samples obtained from 263 case subjects and 263 control subjects to determine their genotypes for CYP1A1 and GSTM1. Control subjects were matched with case subjects by ethnic background, age and gender. Results: The frequencies of the variant CYP1A1 genotypes (CYP1A1C) and GSTM1-null in lung cancer groups were higher than those in control groups (38.4% vs. 28.5% and 57.8% vs. 48.0%). The individuals who carried with CYP1A1C genotype had a significantly higher risk of lung cancer (OR=1.56, 95% CI=1.08 to 2.25, P=0.016) than those who carried with non-variation CYP1A1 genotype. The ones who carried with GSTM1-null genotype also had a significantly higher risk of lung cancer (OR=1.49, 95% CI=1.06 to 2.10, P=0.023) than those who carried with GSTM1-present genotype. When combination of polymorphisms of CYP1A1 and GSTM1 genotypes was analyzed, the risk of lung cancer for combination of CYP1A1C and GSTM1-null genotypes was increased significantly (OR=2.084, 95% CI=1.27 to 3.42, P=0.003). Susceptibility to lung cancer was related to smoking (OR=2.10, 95% CI=1.48 to 2.98, P=0.000). Considering smoking status, the risk of lung cancer for combination of smoking and CYP1A1C genotype was remarkably increased (OR=2.76, 95% CI=1.74 to 4.37, P=0.000). It was the same case with combination of smoking and GSTM1-null genotype (OR=4.38, 95% CI=2.35 to 8.15, P=0.000). Conclusion: The polymorphisms of CYP1A1C genotype and GSTM1-null are the risk factors of lung cancer in the Mongolian population in Inner Mongolia Region of China. Smoking is also related to susceptibility to lung cancer. There may be a synergetic interaction between CYP1A1C and GSTM1-null in the elevated susceptibility of lung cancer. Smoking may have a synergetic interaction with CYP1A1C and GSTM1-null in the elevated susceptibility of lung cancer.