TY - JOUR

T1 - Polymorphisms of GSTM1, GSTT1, GSTP1 genes and chromosomal aberrations in lung cancer patients

AU - Minina, Varvara I.

AU - Soboleva, Olga A.

AU - Glushkov, Andrey N.

AU - Voronina, Elena N.

AU - Sokolova, Ekaterina A.

AU - Bakanova, Marina L.

AU - Savchenko, Yana A.

AU - Ryzhkova, Anastasia V.

AU - Titov, Ruslan A.

AU - Druzhinin, Vladimir G.

AU - Sinitsky, Maxim Yu

AU - Asanov, Maxim A.

N1 - Publisher Copyright: © 2017, Springer-Verlag GmbH Germany.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Carcinogenesis

KW - Chromosomal aberrations

KW - Gene polymorphisms

KW - GST supergene family

KW - Lung cancer

KW - Xenobiotic biotransformation

KW - S-TRANSFERASE M1

KW - INDIVIDUAL SUSCEPTIBILITY

KW - CYTOGENETIC BIOMARKERS

KW - HEALTHY HUMANS

KW - RISK

KW - DAMAGE

KW - AIR-POLLUTION

KW - MOLECULAR EPIDEMIOLOGY

KW - DNA-REPAIR

KW - LYMPHOCYTES

UR - http://www.scopus.com/inward/record.url?scp=85026766650&partnerID=8YFLogxK

U2 - 10.1007/s00432-017-2486-3

DO - 10.1007/s00432-017-2486-3

M3 - Article

C2 - 28770368

AN - SCOPUS:85026766650

VL - 143

SP - 2235

EP - 2243

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 11

ER -