Risk for K-ras gene mutations in smoking-induced lung cancer is associated with cytochrome P4501A1 and glutathione S-transferase micro1 polymorphisms.

Polycyclic aromatic hydrocarbons (PAHs) and other tobacco-related carcinogens are oxidized by phase I enzymes into reactive metabolites that are then detoxified by phase II enzymes. These findings suggested that polymorphisms in genes controlling metabolism of carcinogens underlie individual variations in cancer susceptibility. Moreover, it is unclear whether there is a relation between genetically determined individual susceptibilities and target gene mutations in lung carcinogenesis. We examined K-ras mutations in relation to polymorphisms in the cytochrome P4501A1 (CYP1A1) and glutathione S-transferase micro1 (GSTM1) genes in 246 patients with lung adenocarcinoma and 167 patients with lung squamous cell carcinoma. K-ras mutations were found in 33 of 413 (8.0%) tumors, and all K-ras gene mutations were found in habitual smokers, 110 non-smokers were excluded from final analysis. Among smokers with lung adenocarcinoma, K-ras mutations occurred with greater frequency in patients with the GSTM1(-) genotype than in those with the GSTM1(+) genotype. Patients with a combination of the CYP1A1 m1/m2 and GSTM1(-) genotypes showed an increased probability of having mutated K-ras genes (OR, 6.00; p=0.031; 95% CI, 1.18-30.62) in comparison to those with the CYP1A1 m1/m1 and GSTM1(+) genotypes. The impact of combined genotypes of the CYP1A1 Ile/Val polymorphism and GSTM1 on mutation of K-ras was also analyzed, and a higher risk of having a mutated K-ras gene was found for both the CYP1A1 Ile/Ile and GSTM1(-) (OR, 6.32; p=0.021; 95% CI, 1.33-30.19) and CYP1A1 Ile/Val and GSTM1(-) (OR, 6.09; p=0.042; 95% CI, 1.07-34.72) genotype combinations in patients with adenocarcinoma. There was no significant association for squamous cell carcinoma. In conclusion, these findings suggest that K-ras mutations in smokers with lung adenocarcinoma may be due in part to accumulation of carcinogens, which is not adequately detoxified in individuals with certain CYP1A1 genotypes and the GSTM1(-) genotype.

[Genetic investigations for lung carcinoma].

Lung carcinoma is a common malignant disease in adults. Various genetic changes associated with small cell and non-small cell lung carcinoma are now known. There are two types of genetic change which influence tumor growth and patient prognosis. Among oncogenes, c-myc, K-ras, and erbB-2 are considered to play important roles in lung carcinogenesis. The p53 suppressor gene is highly expressed in small and non-small cell carcinoma. To differentiate between double primary lung carcinomas and intrapulmonary metastasis, or between primary lung carcinoma and metastatic lung tumor, the analysis of gene mutations, such as of p53 and K-ras, appears to be very useful.

A case of mixed connective tissue disease complicated with thymic carcinoma and Hashimoto's thyroiditis.

We report the case of a 63-year-old woman who suffered from mixed connective tissue disease (MCTD) complicated with thymic carcinoma and Hashimoto's thyroiditis. Although many systemic syndromes associated with thymoma and thymic carcinoma, i.e., myasthenia gravis, pure red cell aplasia, hypogammaglobulinemia, and Hashimoto's thyroiditis, are known, this is the first report of MCTD complicated with thymic carcinoma. It was suggested that MCTD may be a paraneoplastic syndrome associated with thymic carcinoma.

Synchronous multicentric thymona: report of a case.

We report a case of multiple thymoma with different histological subtypes, not associated with myasthenia gravis. We describe the histological findings, especially the results of immunohistochemical staining, which support the possibility of multicentric thymoma. The validity of extended thymectomy is also discussed.