Glutathione S-transferase mu1 null genotype is associated with K-ras gene mutation in lung adenocarcinoma among smokers.
Glutathione S-transferase mu1 (GSTM1) plays a role in the detoxification of benzo[a]pyrene (BP) diol epoxide in tobacco smoke. Individuals who genetically lack the GSTM1 gene are likely to have an increased risk of smoking-related lung cancers, however, the target oncogenes for mutation are unknown. To investigate the relation between GSTM1 genotype and K-ras gene mutation we examined 193 adenocarcinomas and 119 squamous cell carcinomas of lung. The GSTM1 genotype was determined by PCR and K-ras gene mutations at codons 12 and 13 were detected by dot-blot hybridization analysis using sequence-specific oligonucleotide probes. K-ras gene mutations were found in 29 of 312 (9.3%) tumors. All of them arose in patients who were habitual smokers. Mutations of the K-ras gene were detected in 6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and GSTM1(-) genotypes, respectively, and the difference was statistically significant. These findings suggest that the cause of K-ras gene mutation in smokers with lung adenocarcinoma may be in part an accumulation of BP diol epoxide which is not well detoxified in individuals with the GSTM1 null genotype.
Matsuzoe
D
D
Second Department of Surgery, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonanku, Fukuoka 814-0180, Japan.
Hideshima
T
T
Iwasaki
A
A
Yoneda
S
S
Kawahara
K
K
Shirakusa
T
T
Kimura
A
A
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D003062:Codon; D017931:DNA Primers; D005260:Female; D011905:Genes, ras; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking / Q000235:genetics*
D003062:Codon; D017931:DNA Primers; D005982:Glutathione Transferase