Glutathione S-transferase mu1 null genotype is associated with K-ras gene mutation in lung adenocarcinoma among smokers.

Abstract

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.

• Authors: D Matsuzoe, T Hideshima, A Iwasaki, S Yoneda, K Kawahara, T Shirakusa, A Kimura
• Journal: Carcinogenesis (Carcinogenesis) Vol. 22 Issue 8 Pg. 1327-30 (Aug 2001) ISSN: 0143-3334 [Print] England
• PMID: 11470766 (Publication Type: Journal Article)

Chemical References

• Codon
• DNA Primers
• Glutathione Transferase
• glutathione S-transferase M1

Topics

• Adenocarcinoma (enzymology, genetics)
• Base Sequence
• Codon
• DNA Primers
• Female
• Genes, ras
• Genotype
• Glutathione Transferase (genetics)
• Humans
• Lung Neoplasms (enzymology, genetics)
• Male
• Middle Aged
• Mutation
• Smoking (genetics)