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

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.

GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: A meta-analysis

“…Six studies evaluating GSTM1, GSTT1, and GSTP1 genotypes and their association with risk of lung cancer met the inclusion criteria for the meta-analysis [41][42][43][44][45][46]. Table 1 provides a summary of each gene's name and chromosomal location.…”

“…The papers were then reviewed to identify casecontrol studies in Asian populations. A total of 11 case-control studies [36][37][38][39][40][41][42][43][44][45][46] were found. Five studies [36][37][38][39][40] were excluded because there was no exposure assessment and no evidence provided in the study that indoor air pollution from any source made an important contribution to lung cancer.…”

“…Five studies [36][37][38][39][40] were excluded because there was no exposure assessment and no evidence provided in the study that indoor air pollution from any source made an important contribution to lung cancer. The remaining 6 studies [41][42][43][44][45][46] satisfied all inclusion criteria, and data related to study design, geographic location, population setting, case selection, control selection, genotyping method, Hardy-Weinberg equilibrium, type of exposure, exposure assessment, smoking, and number of genotyped cases and controls were extracted.…”

“…Overall, one study utilized a quantitative exposure assessment [41], one a qualitative exposure assessment [42], and the presence of indoor air pollution was determined for four studies [43][44][45][46]. Lan et al's [41] study was in Xuan Wei, where more than 95% of the population was exposed to coal and a substantial portion of lung cancer has been attributed to indoor coal use [14;47].…”

“…Similarly more than 95% of the population in the Shenyang study reported by Yang et al [45] was also exposed to coal [45;48], and epidemiologic studies have shown that coal exposure is associated with increased risk of lung cancer in Shenyang [49][50][51]. Approximately 80% of the population in Changsha City in the Hunan study for nonsmoking lung cancer cases and controls by Chen et al [43] were exposed to coal up until 1997 (Han-chun Chen, personal communication), and about 80% of the population in the Beijing study by Wang et al [46] used coal in their homes (Jingwen Wang, personal communication). Although formal risk estimates have not been published for coal use and lung cancer in these two studies, it is highly likely that this exposure is associated with risk of lung cancer [17].…”