Association between Glutathione S-transferase Gene Polymorphisms and Lung Squamous Cell Carcinoma in Patients with Chronic Obstructive Pulmonary Disease: A Case-control Study

Mengdan Zhao, Jiqing Hao

Show Less

¹ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China,

PAR 2025 , 9(6), 104–118; https://doi.org/10.26689/par.v9i6.12909

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

Abstract

This case-control study evaluated the frequency of Glutathione S-transferase Mu 1 (GSTM1) deletion and Glutathione S-transferase Alpha 1 (GSTA1) mutation in chronic obstructive pulmonary disease (COPD) patients, whether they had concomitant lung squamous cell carcinoma (LSCC) or not, to assess their connection with cancer susceptibility. By means of multivariate logistic regression analysis, the GSTM1 null genotype serves as a significant standalone risk factor for LSCC, in addition to variables like age, smoking history, emphysema, body mass index (BMI), albumin level, and neutrophil-to-lymphocyte ratio (NLR). A predictive model incorporating these factors demonstrated superior discriminative ability compared to the established COPD Lung Cancer Screening Score (COPD-LUCSS).

References

Sung H, Ferlay J, Siegel R, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71(3): 209–249.

Nicholson A, Tsao M, Beasley M, et al., 2022, The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol, 17(3): 362–387.

Torres J, Bastarrika G, Wisnivesky J, et al, 2007, Assessing the Relationship Between Lung Cancer Risk and Emphysema Detected on Low-Dose CT of the Chest. Chest, 132(6): 1932–1938.

Torres J, Marín J, Casanova C, et al., 2011, Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: Incidence and Predicting Factors. Am J Respir Crit Care Med, 184(8): 913–919.

Mannino D, Aguayo S, Petty T, et al., 2003, Low Lung Function and Incident Lung Cancer in the United States: Data From the First National Health and Nutrition Examination Survey Follow-up. Arch Intern Med, 163(12): 1475–1480.

Young R, Hopkins R, 2012, Diagnosing COPD and Targeted Lung Cancer Screening. Eur Respir J, 40(4): 1063–1064.

Celli B, Fabbri L, Criner G, et al., 2022, Definition and Nomenclature of Chronic Obstructive Pulmonary Disease: Time for Its Revision. Am J Respir Crit Care Med, 206(11): 1317–1325.

Adeloye D, Song P, Zhu Y, et al., 2022, Global, Regional, and National Prevalence of, and Risk Factors for, Chronic Obstructive Pulmonary Disease (COPD) in 2019: A Systematic Review and Modelling Analysis. Lancet Respir Med, 10(5): 447–458.

Young R, Hopkins R, Christmas T, et al., 2009, COPD Prevalence Is Increased in Lung Cancer, Independent of Age, Sex and Smoking History. Eur Respir J, 34(2): 380–386.

Wilson D, Weissfeld J, Balkan A, et al., 2008, Association of Radiographic Emphysema and Airflow Obstruction With Lung Cancer. Am J Respir Crit Care Med, 178(7): 738–744.

Qi C, Sun S, Xiong X, 2022, From COPD to Lung Cancer: Mechanisms Linking, Diagnosis, Treatment, and Prognosis. Int J Chron Obstruct Pulmon Dis, 17: 2603–2621.

Singh R, Reindl K, 2021, Glutathione S-Transferases in Cancer. Antioxidants, 10(5): 701.

Pathak A, Husain N, Kant S, et al., 2021, Independent and Interactive Effect of CYPs and GSTs Genetic Variants and Tobacco Smoking on the Risk of Non-Small Cell Lung Carcinoma. Arch Med Res, 52(7): 719–730.

Alexandrov K, 2002, CYP1A1 and GSTM1 Genotypes Affect Benzo[a]pyrene DNA Adducts in Smokers’ Lung: Comparison With Aromatic/Hydrophobic Adduct Formation. Carcinogenesis, 23(12): 1969–1977.

Norppa H, 2004, Cytogenetic Biomarkers and Genetic Polymorphisms. Toxicol Lett, 149(1–3): 309–334.

Ramzy M, Solliman M, Abdel-Hafiz H, et al., 2011, Genetic Polymorphism of GSTM1 and GSTP1 in Lung Cancer in Egypt. Public Health, 3(1): 41–51.

Romero L, Andrews K, Ng L, et al., 2006, Human GSTA1-1 Reduces c-Jun N-Terminal Kinase Signalling and Apoptosis in Caco-2 Cells. Biochem J, 400(1): 135–141.

Mlakar V, Curtis P, Armengol M, et al., 2021, The Analysis of GSTA1 Promoter Genetic and Functional Diversity of Human Populations. Sci Rep, 11(1): 5038.

Li S, Li M, Wu J, et al., 2024, Developing and Validating a Clinlabomics-Based Machine-Learning Model for Early Detection of Retinal Detachment in Patients With High Myopia. J Transl Med, 22(1): 405.

Wijma K, Wijma B, Zar M, 1998, Psychometric Aspects of the W-DEQ: A New Questionnaire for the Measurement of Fear of Childbirth. J Psychosom Obstet Gynecol, 19(2): 84–97.

Ford J, 2000, Glutathione S-Transferase M1 Polymorphism and Lung Cancer Risk in African-Americans. Carcinogenesis, 21(11): 1971–1975.

Dey T, Dutta P, Kalita J, et al., 2015, Glutathione S-Transferase Gene Polymorphism and Lung Cancer in Indian Population: A Meta-Analysis of Case-Control Studies. Curr Sci, 109(3): 536–540.

Young R, Hopkins R, Hay J, et al., 2011, GSTM1 Null Genotype in COPD and Lung Cancer: Evidence of a Modifier or Confounding Effect? Appl Clin Genet, 137–144.

Sharma N, Singh A, Singh N, et al., 2015, Genetic Polymorphisms in GSTM1, GSTT1 and GSTP1 Genes and Risk of Lung Cancer in a North Indian Population. Cancer Epidemiol, 39(6): 947–955.

Lee K, Kang D, Clapper M, et al., 2008, CYP1A1, GSTM1, and GSTT1 Polymorphisms, Smoking, and Lung Cancer Risk in a Pooled Analysis Among Asian Populations. Cancer Epidemiol Biomarkers Prev, 17(5): 1120–1126.

López-Cima M, Álvarez-Avellón S, Pascual T, et al., 2012, Genetic Polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1 Metabolic Genes and Risk of Lung Cancer in Asturias. BMC Cancer, 12: 433.

Sørensen M, Autrup H, Tjønneland A, et al., 2005, Genetic Polymorphisms in CYP1B1, GSTA1, NQO1 and NAT2 and the Risk of Lung Cancer. Cancer Lett, 221(2): 185–190.

Wang W, Liu F, Wang C, et al., 2017, Glutathione S-Transferase A1 Mediates Nicotine-Induced Lung Cancer Cell Metastasis by Promoting Epithelial-Mesenchymal Transition. Exp Ther Med, 14(2): 1783–1788.

Liu H, Yang Z, Zang L, et al., 2018, Downregulation of Glutathione S-Transferase A1 Suppressed Tumor Growth and Induced Cell Apoptosis in A549 Cell Line. Oncol Lett, 16(1): 467–474.

Sandelin M, Mindus S, Thuresson M, et al., 2018, Factors Associated With Lung Cancer in COPD Patients. Int J Chron Obstruct Pulmon Dis, 13: 1833–1839.

Chen J, Ke K, Liu Z, et al., 2023, Body Mass Index and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies. Nutr Cancer, 75(4): 1051–1064.

Yu D, Zheng W, Johansson M, et al., 2018, Overall and Central Obesity and Risk of Lung Cancer: A Pooled Analysis. JNCI J Natl Cancer Inst, 110(8): 831–842.

Kawai S, Lin Y, Tsuge H, et al., 2024, Body Mass Index and Lung Cancer Risk: Pooled Analysis of 10 Prospective Cohort Studies in Japan. Cancer Sci, 115(4): 1346–1359.

Yong P, Sigel K, de-Torres J, et al., 2019, The Effect of Radiographic Emphysema in Assessing Lung Cancer Risk. Thorax, 74(9): 858–864.

Wang W, Xie M, Dou S, et al., 2018, The Link Between Chronic Obstructive Pulmonary Disease Phenotypes and Histological Subtypes of Lung Cancer: A Case–Control Study. Int J Chron Obstruct Pulmon Dis, 13: 1167–1175.

Yang Z, Zheng Y, Wu Z, et al., 2021, Association Between Pre-Diagnostic Serum Albumin and Cancer Risk: Results From a Prospective Population-Based Study. Cancer Med, 10(12): 4054–4065.

Sprague B, Trentham-Dietz A, Klein B, et al., 2008, Physical Activity, White Blood Cell Count, and Lung Cancer Risk in a Prospective Cohort Study. Cancer Epidemiol Biomarkers Prev, 17(10): 2714–2722.

Zahorec R, 2001, Ratio of Neutrophil to Lymphocyte Counts—Rapid and Simple Parameter of Systemic Inflammation and Stress in Critically Ill. Bratisl Med J, 102(1): 5–14.

Ma A, Wang G, Du Y, et al., 2022, The Clinical Relevance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Chronic Obstructive Pulmonary Disease With Lung Cancer. Front Oncol, 12: 902955.

Bronte V, Brandau S, Chen S, et al., 2016, Recommendations for Myeloid-Derived Suppressor Cell Nomenclature and Characterization Standards. Nat Commun, 7(1): 12150.

Sarraf K, Belcher E, Raevsky E, et al., 2009, Neutrophil/Lymphocyte Ratio and Its Association With Survival After Complete Resection in Non–Small Cell Lung Cancer. J Thorac Cardiovasc Surg, 137(2): 425–428.

de-Torres J, Wilson D, Sanchez-Salcedo P, et al., 2015, Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: Development and Validation of the COPD Lung Cancer Screening Score. Am J Respir Crit Care Med, 191(3): 285–291.

Previous article in this issue

Next article in this issue