Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 11/2017

01-11-2017 | Original Article – Cancer Research

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

Authors: 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

Published in: Journal of Cancer Research and Clinical Oncology | Issue 11/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
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
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
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
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
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
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
Metadata
Title
Polymorphisms of GSTM1, GSTT1, GSTP1 genes and chromosomal aberrations in lung cancer patients
Authors
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
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 11/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-017-2486-3

Other articles of this Issue 11/2017

Journal of Cancer Research and Clinical Oncology 11/2017 Go to the issue

Original Article – Cancer Research

Efficient targeting of CD13 on cancer cells by the immunotoxin scFv13–ETA′ and the bispecific scFv [13xds16]

Original Article – Cancer Research

Disseminated tumor cells are not associated with established risk factors, L1CAM immunoreactivity and outcome in endometrial carcinoma

Original Article – Clinical Oncology

Prognostic implications of human papillomavirus status for patients with non-oropharyngeal head and neck squamous cell carcinomas

Original Article – Clinical Oncology

The combination of preoperative PET/CT and sentinel lymph node biopsy in the surgical management of early-stage cervical cancer

Original Article – Cancer Research

Induction of alpha-methylacyl-CoA racemase by miR-138 via up-regulation of β-catenin in prostate cancer cells

Review – Clinical Oncology

Methodological quality evaluation of systematic reviews or meta-analyses on ERCC1 in non-small cell lung cancer: a systematic review
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits