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

Glutathione S-transferase mul (GSTM1) plays a role in the detoxification of benzo[a]pyrene (BP) diol epoxide in tobacco smoke. Individuals who genetic ally lack the GSTM1 gene are likely to have an increased risk of smoking-re lated 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 3 12 (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, respect ively, and the difference was statistically significant. These findings sug gest that the cause of K-ras gene mutation in smokers with lung adenocarcin oma may be in part an accumulation of BP diol epoxide which is not well det oxified in individuals with the GSTM1 null genotype.