Genetic Polymorphisms of Phase II Metabolic Enzymes and Lung Cancer Susceptibility in a Population of Central South China

Han-Chun Chen,Yan-Fei Cao,Jia Liu,Wei-Xin Hu,Ji Zhang,Xin-Fa Liu,Qing-Xia Liu

doi:10.1155/2006/436497

Han-Chun Chen, Yan-Fei Cao + Show 5 more

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https://doi.org/10.1155/2006/436497

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Journal: Disease markers	Publication Date: Jan 1, 2006
Citations: 57	License type: CC BY 3.0

Affiliation: Central South University, South University

Abstract

A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/−), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/−) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China.

Highlights

Both environmental and genetic factors are considered important in the etiology of human tumors
To evaluate the risk factors of lung cancer in non-smoking Chinese population, we epidemiologically investigated the relationship of genetic polymorphisms of phase II metabolic enzyme family members GSTM1, GSTT1, GSTP1 and N-acetyltransferase 2 (NAT2) and risk of lung cancer in non-smoking Han ethnic population in Hunan Province of China by PCR and PCR-restriction fragment length polymorphism (RFLP) analysis for the first time
No obvious variation in frequencies of GSTP1 genotype (AA and AG+GG) and NAT2 genotype existed between patients and healthy controls (P > 0.05), but a distinct correlation was observed between lung cancer and the genotypes of combination of GSTM1(-) and GSTT1(-) (P = 0.000), GSTP1(AG+GG) and GSTM1(-) (P = 0.006), as well as GSTP1(AG+GG) and GSTT1(-) (P = 0.003)

Summary

Introduction

Both environmental and genetic factors are considered important in the etiology of human tumors. The risk of cancer correlated with exposures to exogenous xenobiotics or endogenous substances may be modified by genetic variation in metabolic detoxification activ-. Phase II biotransformation enzymes generally act as inactivating enzymes to catalyze the binding of intermediary metabolites to cofactors, transform them into more hydrophilic products and facilitate their elimination. Both GSTs and NATs are phase II transformation enzymes involved in the detoxification of hazardous agents [2]. GSTM1 may act as a determinant factor in susceptibility to the related disease and may be a risk factor for cancer [4]. Chen et al / Genetic polymorphisms of phase II metabolic enzymes and lung cancer susceptibility

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Conclusion