Cancer Res Treat.  2003 Dec;35(6):483-488.

Genetic Polymorphism of Epoxide Hydrolase and GSTM1 in Lung Cancer Susceptibility of Korean Population

• Hwang JH
• Kim KS
• Kim YI
• Kim EJ
• Park KH
• Cho GJ
• Ju JY
• Lim SC
• Kim YC
• Park KO
• Park JT
• Ahn SJ

Abstract

PURPOSE
Although 80~90% of patients with lung cancer are smokers, only 11% of smokers develop lung cancer. Genetic susceptibility according to the polymorphism of the epoxide hydrolase (mEPHX) gene and homozygous deletion of GSTM1 (M1 subunit of Glutathione S transferase) was studied in this case control study. MATERIALS AND METHODS: Genomic DNA from 76 subjects with lung cancer (40 squamous cell carcinoma, 13 adenocarcinoma, 10 subtype undetermined non-small cell lung cancer, and 13 small cell lung carcinoma) and 62 age- matched controls were extracted from peripheral white blood cells. PCR and RFLP (restriction fragments length polymorphism) with restriction enzyme (RsaI) and automatic sequencing were used for mEPHX genotyping (T-->C, Tyr113His) in exon 3 and (A-->G, His139Arg) in exon 4. Looking for homozygous deletions of GSTM1, multiplex PCR with primers for the GSTM1 gene and coagulation factor V gene (as positive control) were performed. RESULTS: The age distribution between the cancer and control groups were similar (63.6 7.2 vs. 61.1 7.9 years). The lung cancer group, however, had more smokers (73.3%, 44/60) than the control group (21/54, 38.9%, p<0.001). The rate of homozygous deletion of the GSTM1 gene was significantly higher in the lung cancer group (65.8%, 50/76) than in the control group (46.8%, 29/62, p<0.05), causing the relative risk of GSTM1 deletion for lung cancer as 2.19 (95% CI: 1.10~4.35, p=0.02). Among 118 subjects whose mEPHX gene polymorphisms were studied, 62 (52.5%) subjects showed genotypes with slow enzyme activity while 45 (38.1%) showed normal enzyme activity and 11 (9.3%) showed fast enzyme activity. There was no significant difference in the distribution of mEPHX gene polymorphisms between the two groups. CONCLUSION: The homozygous deletion of the GSTM1 gene was associated with high lung cancer susceptibility, whereas the mEPHX genotype showed no significant connection with risk of lung cancer in a sample Korean population.

Keyword

Lung neoplasm; Genetic polymorphism; Epoxide hydrolase; Glutathione S transferase

MeSH Terms

Adenocarcinoma
Age Distribution
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Case-Control Studies
DNA
Exons
Factor V
Genetic Predisposition to Disease
Genotype
Glutathione
Glutathione Transferase
Humans
Leukocytes
Lung Neoplasms*
Lung*
Multiplex Polymerase Chain Reaction
Polymerase Chain Reaction
Polymorphism, Genetic*
Polymorphism, Restriction Fragment Length
DNA
Factor V
Glutathione
Glutathione Transferase