Glutathione S-transferase mu 1 null genotype is associated with K-ras gene mutation in lung adenocarcinoma among smokers

• Published in: Carcinogenesis (New York) Vol. 22; no. 8; pp. 1327 - 1329
• Main Authors: Matsuzoe, Daisuke, Hideshima, Teru, Iwasaki, Akinori, Yoneda, Satoshi, Kawahara, Katsunobu, Shirakusa, Takayuki, Kimura, Akinori
• Format: Journal Article
• Language: English
• Published: 01.08.2001
• Subjects: K-ras gene
• ISSN: 0143-3334
• DOI: 10.1093/carcin/22.8.1327

Glutathione S-transferase mu 1 (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.