Varvara I Minina1,2, Olga A Soboleva3, Andrey N Glushkov3, Elena N Voronina4, Ekaterina A Sokolova4,5, Marina L Bakanova3, Yana A Savchenko3, Anastasia V Ryzhkova3, Ruslan A Titov3, Vladimir G Druzhinin3,6, Maxim Yu Sinitsky3,7, Maxim A Asanov3. 1. Federal State Budget Scientific Institution, The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences, Sovetskiy Ave 18, Kemerovo, 650065, Russian Federation. vminina@mail.ru. 2. Department of Genetics, Biology Faculty, Kemerovo State University, Krasnaya St 6, Kemerovo, 650043, Russian Federation. vminina@mail.ru. 3. Federal State Budget Scientific Institution, The Federal Research Center of Coal and Coal Chemistry of Siberian Branch of the Russian Academy of Sciences, Sovetskiy Ave 18, Kemerovo, 650065, Russian Federation. 4. Institute of Chemical Biology and Fundamental Medicine of SB RAS, Lavrentiev Ave 8, Novosibirsk, 630090, Russian Federation. 5. Novosibirsk State University, Pirogova St 2, Novosibirsk, 630090, Russian Federation. 6. Department of Genetics, Biology Faculty, Kemerovo State University, Krasnaya St 6, Kemerovo, 650043, Russian Federation. 7. Laboratory of Genome Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Sosnovy Blvd 6, Kemerovo, 650002, Russian Federation.
Abstract
PURPOSE: To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancer patients and healthy residents in Russian Federation. METHODS: 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancer patients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA). RESULTS: We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancer patients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancer patients harbouring the GSTM1 del polymorphism. CONCLUSIONS: CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.
PURPOSE: To study the potential links between genetic polymorphisms in the GSTT1, GSTM1, GSTP1 genes and the frequency of chromosomal aberrations (CAs) in lung cancerpatients and healthy residents in Russian Federation. METHODS: 200 cells in well-spread metaphase with 46 chromosomes were examined for 353 newly diagnosed lung cancerpatients (males) who received medical treatment in the Kemerovo Regional Oncology Center (Kemerovo, Russian Federation), and 300 healthy males from Kemerovo, Russian Federation. The polymorphisms of the GSTM1 del and GSTT1 del genes were analysed by multiplex PCR. Genotyping of the polymorphic variants in the GSTP1 (A313G, T341C) gene was performed using Real-time PCR with competing TaqMan probes complementary to the polymorphic DNA sites. The data analysis was performed using software STATISTICA 8.0 (StatSoft Inc., USA). RESULTS: We discovered that a GSTM1 del polymorphism increases the frequency of chromosomal damage in smoking patients with lung cancer, a general group of lung cancerpatients, donors with non-small cell lung cancer and patients in the latest stages of the malignant process. The synergetic effects of occupational exposure and the malignant process can induce some modifications in the cytogenetic status in lung cancerpatients harbouring the GSTM1 del polymorphism. CONCLUSIONS: CAs in peripheral blood lymphocytes can be used as biomarkers of the early biological effects of exposure to genotoxic carcinogens and may predict future cancer incidence in several epidemiologic studies. Genetic changes in genes encoding phase II detoxification enzymes are linked to decreases in the metabolic detoxification of environmentally derived genotoxic carcinogens.
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