nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

02.08.2017 | Original Article – Cancer Research

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

verfasst von: Varvara I. Minina, Olga A. Soboleva, Andrey N. Glushkov, Elena N. Voronina, Ekaterina A. Sokolova, Marina L. Bakanova, Yana A. Savchenko, Anastasia V. Ryzhkova, Ruslan A. Titov, Vladimir G. Druzhinin, Maxim Yu. Sinitsky, Maxim A. Asanov

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2017

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Ada A, Demiroglu C, Yilmazer M et al (2013) Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic hydrocarbons: association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 gene polymorphisms. Arh Hig Rada Toksikol 64(3):359–369PubMed

Anantharaman D, Samant TA, Sen S, Mahimkar MB (2011) Polymorphisms in tobacco metabolism and DNA repair genes modulate oral precancer and cancer risk. Oral Oncol 47:866–872CrossRefPubMed

Benhamou S, Lee WJ, Alexandrie AK et al (2002) Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk. Carcinogenesis 23:1343–1350CrossRefPubMed

Boffetta P, van der Hel O, Norppa H et al (2007) Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe. Am J Epidemiol 165:36–43CrossRefPubMed

Bonassi S, Ceppi M, Fontana V, Merlo F (1994) Multiple regression analysis of cytogenetic human data. Mutat Res 313:69–80CrossRefPubMed

Bonassi S, Norppa H, Ceppi M et al (2008) Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22,358 subjects in 11 countries. Carcinogenesis 29:1178–1183CrossRefPubMedPubMedCentral

Brogger A, Hagmar L, Hansteen IL et al (1990) An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Nordic Study Group on the Health Risk of Chromosome Damage. Cancer Genet Cytogenet 45:85–92CrossRefPubMed

Cajas-Salazar N, Sierra-Torres CH, Salama S et al (2003) Combined effect of MPO, GSTM1 and GSTT1 polymorphisms on chromosome aberrations and lung cancer risk. Int J Hyg Environ Health 206:473–483CrossRefPubMed

Druzhinin VG (2003) Quantitative characteristics of the frequency of chromosomal aberrations in a group of residents of a large western Siberian industrial region. Russ J Genet 39:1161–1167CrossRef

Druzhinin V, Bakanova M, Fucic A, Golovina T, Savchenko Y, Sinitsky M, Volobaev V (2016) Lymphocytes with multiple chromosomal damages in a large cohort of West Siberia residents: results of long-term monitoring. Mutat Res 784–785:1–7CrossRefPubMed

Dusinska M, Staruchova M, Horska A, Smolkova B, Collins A, Bonassi S, Volkovova K (2012) Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies. Mutat Res 736:130–137CrossRefPubMed

Garte S, Gaspari L, Alexandrie AK et al (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 10:1239–1248PubMed

Goldstraw P (2013) New staging system: how does it affect our practice? J Clin Oncol 31:984–991CrossRefPubMed

Hagmar L, Stromberg U, Bonassi S et al (2004) Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts. Cancer Res 64:2258–2263CrossRefPubMed

Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61:154–166CrossRefPubMed

Hemminki K, Musak L, Vymetalkova V et al (2014) Cyclin D1 splice site variant triggers chromosomal aberrations in healthy humans. Leukemia 28:721–722CrossRefPubMed

Hemminki K, Frank C, Försti A et al (2015) Metabolic gene variants associated with chromosomal aberrations in healthy humans. Genes Chromosomes Cancer 54:260–266CrossRefPubMed

Hersh CP, DeMeo DL, Reilly JJ, Silverman EK (2007) Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery. Respir Res 8:59CrossRefPubMedPubMedCentral

Hoyos-Giraldo LS, Escobar-Hoyos LF, Reyes-Carvajal I et al (2013) The effect of genetic admixture in an association study: genetic polymorphisms and chromosome aberrations in a Colombian population exposed to organic solvents. Ann Hum Genet 77:308–320CrossRefPubMed

Kadioglu E, Kocabas NA, Demircigil GC et al (2012) Assessment of individual susceptibility to baseline DNA and cytogenetic damage in a healthy Turkish population: evaluation with lifestyle factors. Genet Test Mol Biomarkers 16:1157–1164CrossRefPubMedPubMedCentral

Knudsen LE, Norppa H, Gamborg MO et al (1999) Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2. Cancer Epidemiol Biomark Prev 8:303–310

Kumar A, Yadav A, Giri SK, Dev K, Gautam SK, Gupta R, Aggarwal N (2011) Effect of genetic polymorphism of GSTM1 and GSTT1 genotypes on cytogenetic biomarkers among coaltar workers. Environ Toxicol Pharmacol 32:128–135CrossRefPubMed

Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res 463:247–283CrossRefPubMed

Lee SA, Fowke JH, Lu W et al (2008) Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk. Am J Clin Nutr 87:753–760PubMed

MacIntyre EA, Brauer M, Melén E et al (2014) GSTP1 and TNF gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) study. Environ Health Perspect 122:418–424PubMedPubMedCentral

Mielzynska-Svach D, Blaszczyk E, Butkiewicz D, Durzynska J, Rydzanicz M (2013) Influence of genetic polymorphisms on biomarkers of exposure and effects in children living in Upper Silesia. Mutagenesis 28:591–599CrossRefPubMed

Minina VI, Savchenko IA, Bakanova ML et al (2011) Contribution of genetic polymorphism to the formation of individual genome sensitivity in workers engaged in heat and power industry. Gig Sanit 5:30–32

Minina VI, Sinitsky MY, Druzhinin VG et al (2016) Chromosome aberrations in peripheral blood lymphocytes of lung cancer patients exposed to radon and air pollution. Eur J Cancer Prev. doi:10.1097/CEJ.0000000000000270 PubMed

Mušák L, Halašová E, Matáková T et al (2009) Comparison of chromosomal aberrations frequency and polymorphism of GSTs genes in workers occupationally exposed to cytostatics or anaesthetics. Interdiscip Toxicol 2:190–194PubMedPubMedCentral

Norppa H (1997) Cytogenetic markers of susceptibility: influence of polymorphic carcinogenme- tabolizing enzymes. Env Health Pers 105:829–835CrossRef

Norppa H (2004) Cytogenetic biomarkers and genetic polymorphisms. Toxicol Lett 149:309–334CrossRefPubMed

Oskina NA, Ermolenko NA, Boyarskih UA et al (2014) Associations between SNPs within antioxidant genes and the risk of prostate cancer in the Siberian region of Russia. Pathol Oncol Res 20:635–640CrossRefPubMed

Palmer CN, Doney AS, Lee SP, Murrie I, Ismail T, Macgregor DF, Mukhopadhyay S (2006) Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak expiratory flow in asthma. Pediatrics 118:710–716CrossRefPubMed

Pan C, Zhu G, Yan Z, Zhou Y, Liu Z (2014) Glutathione S-transferase T1 and M1 polymorphisms are associated with lung cancer risk in a gender-specific manner. Oncol Res Treat 37:164–169CrossRefPubMed

Pliarchopoulou K, Voutsinas G, Papaxoinis G et al (2012) Correlation of CYP1A1, GSTP1 and GSTM1 gene polymorphisms and lung cancer risk among smokers. Oncol Lett 3:1301–1306PubMedPubMedCentral

Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6:733–743PubMed

Rossi AM, Hansteen IL, Skjelbred CF et al (2009) Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1. Environ Health Perspect 117:203–238CrossRefPubMed

Rossner P, Boffetta P, Ceppi M et al (2005) Chromosomal aberration in lymphocytes of healthy subjects and risk of cancer. Environ Health Perspect 113:517–520CrossRefPubMedPubMedCentral

Rotunno M, Lam TK, Vogt A et al (2012) GSTM1 and GSTT1 copy numbers and mRNA expression in lung cancer. Mol Carcinog 51:E142–E150CrossRefPubMedPubMedCentral

Sambrook J, Fritsch E, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

Santovito A, Cervella P, Delpero M (2015) Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage. Ann Hum Biol 24:1–10

Savage JR (1976) Classification and relationships of induced chromosomal structural changes. J Med Genet 13:103–122CrossRefPubMedPubMedCentral

Scarpato R, Hirvonen A, Migliore L, Falck G, Norppa H (1997) Influence of GSTM1 and GSTT1 polymorphisms on the frequency of chromosome aberrations in lymphocytes of smokers and pesticide-exposed greenhouse workers. Mutat Res 389:227–235CrossRefPubMed

Sharma N, Singh A, Singh N, Behera D, Sharma S (2015) Genetic polymorphisms in GSTM1, GSTT1 and GSTP1 genes and risk of lung cancer in a North Indian population. Cancer Epidemiol 39:947–955CrossRefPubMed

Skjelbred C, Svendsen M, Haugan V et al (2011) Influence of GSTM1, GSTT1, GSTP1, NAT1, NAT2, EPHX1, MTR and MTHFR polymorphism on chromosomal aberration frequencies in human lymphocytes. Carcinogenesis 32:399–405CrossRefPubMed

Spitz MR, Wei Q, Dong Q, Amos CI, Wu X (2003) Genetic susceptibility to lung cancer: the role of DNAdamage and repair. Cancer Epidemiol Biomarkers Prev 12:689–698PubMed

Sun KH, Chang KH, Clawson S et al (2011) Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. J Neurochem 118:902–914CrossRefPubMed

Tamer L, Calikoğlu M, Ates NA et al (2004) Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma. Respirology 9:493–498CrossRefPubMed

Vodenkova S, Polivkova Z, Musak L et al (2015) Structural chromosomal aberrations as potential risk markers in incident cancer patients. Mutagenesis 30:557–563CrossRefPubMed

Vodicka P, Kumar R, Stetina R et al (2004) Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant. Environ Mol Mutagen 44:283–292CrossRefPubMed

Vodicka P, Polivkova Z, Sytarova S et al (2010) Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis 31:1238–1241CrossRefPubMed

Zhang H, Wu X, Xiao Y, Chen M, Li Z, Wei X, Tang K (2014) Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer. Eur J Med Res 19:67CrossRefPubMedPubMedCentral

Titel: Polymorphisms of GSTM1, GSTT1, GSTP1 genes and chromosomal aberrations in lung cancer patients
verfasst von: Varvara I. Minina
Olga A. Soboleva
Andrey N. Glushkov
Elena N. Voronina
Ekaterina A. Sokolova
Marina L. Bakanova
Yana A. Savchenko
Anastasia V. Ryzhkova
Ruslan A. Titov
Vladimir G. Druzhinin
Maxim Yu. Sinitsky
Maxim A. Asanov
Publikationsdatum: 02.08.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2017
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-017-2486-3

Springer Medizin

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