Genetic Polymorphism of Cyp2a6 and Cyp2a13 Genes and Environmental Tobacco Smoke Induced Lung Cancer Risk in Indonesian Female Never Smokers

Noni Soeroso; Rozaimah Zain-Hamid; Syamsul Bihar; Setia Putra Tarigan; Fannie Rizki Ananda

doi:10.3889/oamjms.2021.6069

Authors

Noni Soeroso Department of Pulmonology and Respiratory Medicine, Thoracic Oncology Division, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0002-2687-4924
Rozaimah Zain-Hamid Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Syamsul Bihar Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Setia Putra Tarigan Department of Pulmonology and Respiratory Medicine, Thoracic Oncology Division, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0002-6242-7013
Fannie Rizki Ananda Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0002-5982-2194

DOI:

https://doi.org/10.3889/oamjms.2021.6069

Keywords:

Polymorphism of CYP2A6 gene, Polymorphism of CYP213 gene, Polymerase Chain reaction-restriction fragment length polymorphism, Never smokers, Lung cancer

Abstract

BACKGROUND: The presence of nicotine metabolite in the urine of subjects exposed to tobacco smoke represents the nicotine metabolism activity in environmental tobacco smokers. CYP2A6 and CYP2A13 are known as the main enzymes responsible for nicotine metabolism and xenobiotic activity in tobacco smoke-related lung cancer.

AIM: The aim of this study is to analyze the relationship between genetic polymorphism of CYP26 and CYP2A13 genes and environmental tobacco smoke-induced lung cancer risk in Indonesian females never smoker.

METHODS: This is a case-control study with two-stage of distinguishing polymorphism detection. Restriction fragment length polymorphism polymerase chain reaction from venous blood extraction was performed to examine the CYP2A6 and CYP2A13 polymorphism. Logistic regression test in Epi Info-7 software was carried out to examine genetic polymorphism of CYP2A6 and CYP2A13 genes and environmental tobacco smoke-induced lung cancer risk in Indonesian female never smokers.

RESULTS: A total of 203 participants enrolled in this study with the first stage of CYP2A6 polymorphism involved 101 subjects showed no significant correlation between the genotypes of CYP2A6 and the incidence of lung cancer. On the other hand, there was a significant correlation between genotypes of CYP2A13 and the incidence of lung cancer (p < 0.05). People with the genotype CT have a 2.7 higher risk for developing lung cancer compare with genotype CC. Allele *1B was the most common allele in CYP2A6. Allele C has more frequencies and has 0.62 times the risk for developing lung cancer compared with allele T with a wide range of confidence intervals (0.73–3.52).

CONCLUSIONS: There was a significant correlation between polymorphism CYP213 with the incidence of lung cancer among female lung cancer never smoker. However, the results show no significant relationship between CYP2A6 genetic polymorphism and lung cancer incidence.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660 PMid:33538338 DOI: https://doi.org/10.3322/caac.21660

WHO. WHO Global Report on Trends in Prevalence of Tobacco Smoking 2000-2025. 2nd ed. Geneva: WHO; 2018. Available from: http://www.apps.who.int/bookorders [Last accessed on 2021 Feb 15].

Couraud S, Zalcman G, Milleron B, Morin F, Souquet PJ. Lung cancer in never smokers-a review. Eur J Cancer. 2012;48(9):1299-311. https://doi.org/10.1016/j.ejca.2012.03.007 PMid:22464348 DOI: https://doi.org/10.1016/j.ejca.2012.03.007

Samet JM, Avila-Tang E, Boffetta P, Hannan LM, Olivo- Marston S, Thun MJ, et al. Lung cancer in never smokers: Clinical epidemiology and environmental risk factors. Clin Cancer Res. 2009;15(18):5626-45. https://doi.org/10.1158/1078-0432.CCR-09-0376 PMid:19755391 DOI: https://doi.org/10.1158/1078-0432.CCR-09-0376

Bhopal A, Peake MD, Gilligan D, Cosford P. Lung cancer in never-smokers: A hidden disease. J R Soc Med. 2019;112(7):269-71. https://doi.org/10.1177/0141076819843654 PMid:31022354 DOI: https://doi.org/10.1177/0141076819843654

Okazaki I, Ishikawa S, Ando W, Sohara Y. Lung adenocarcinoma in never smokers: Problems of primary prevention from aspects of susceptible genes and carcinogens. Anticancer Res. 2016;36(12):6207-24. https://doi.org/10.21873/anticanres.11215 PMid:27919939 DOI: https://doi.org/10.21873/anticanres.11215

Thomas JL, Guo H, Carmella SG, Balbo S, Han S, Davis A, et al. Metabolites of a tobacco-specific lung carcinogen in children exposed to secondhand or thirdhand tobacco smoke in their homes. Cancer Epidemiol Biomarkers Prev. 2011;20(6):1213-21. PMid:21467230 DOI: https://doi.org/10.1158/1055-9965.EPI-10-1027

Warren G, Singh A. Nicotine and lung cancer. J Carcinog. 2013;12:1. https://doi.org/10.4103/1477-3163.106680 PMid:23599683 DOI: https://doi.org/10.4103/1477-3163.106680

Hecht SS. Lung carcinogenesis by tobacco smoke. Int J Cancer. 2012;131(12):2724-32. https://doi.org/10.1002/ijc.27816 PMid:22945513 DOI: https://doi.org/10.1002/ijc.27816

Benowitz NL, Hukkanen J, Jacob P 3rd. Nicotine chemistry, metabolism, kinetics and biomarkers. Handb Exp Pharmacol. 2009;(192):29-60. https://doi.org/10.1007/978-3-540-69248-5_2 PMid:19184645 DOI: https://doi.org/10.1007/978-3-540-69248-5_2

Johani FH, Majid MS, Azme MH, Nawi AM. Cytochrome P450 2A6 whole-gene deletion (CYP2A6*4) polymorphism reduces risk of lung cancer: A meta-analysis. Tob Induc Dis. 2020;18:50. https://doi.org/10.18332/tid/122465 PMid:32547353 DOI: https://doi.org/10.18332/tid/122465

Wang L, Zang W, Liu J, Xie D, Ji W, Pan Y, et al. Association of CYP2A6*4 with susceptibility of lung cancer: A meta-analysis. PLoS One. 2013;8(4):e59556. https://doi.org/10.1371/journal.pone.0059556 PMid:23585826 DOI: https://doi.org/10.1371/journal.pone.0059556

Ariyoshi N, Miyamoto M, Umetsu Y, Kunitoh H, Dosaka-Akita H, Sawamura Y, et al. Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers. Cancer Epidemiol Biomarkers Prev. 2002;11(9):890-4 PMid:12223434

Wang H, Tan W, Hao B, Miao X, Zhou G, He F, et al. Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Res. 2003;63(22):8057-61. PMid:14633739

Soeroso NN, Zain-Hamid R, Sinaga BY, Sadewa AH, Syafiuddin T, Syahruddin E, et al. Genetic polymorphism of CYP2A6 and its relationship with nicotine metabolism in male bataknese smokers suffered from lung cancer in Indonesia. Open Access Maced J Med Sci. 2018;6(7):1199-205. https://doi.org/10.3889/oamjms.2018.259 PMid:30087722 DOI: https://doi.org/10.3889/oamjms.2018.259

Nakajima M, Yoshida R, Fukami T, McLeod HL, Yokoi T. Novel human CYP2A6 alleles confound gene deletion analysis. FEBS Lett. 2004;569(1-3):75-81. https://doi.org/10.1016/j.febslet.2004.05.053 PMid:15225612 DOI: https://doi.org/10.1016/j.febslet.2004.05.053

Couraud S, Souquet PJ, Paris C, Dô P, Doubre H, Pichon E, et al. BioCAST/IFCT-1002: Epidemiological and molecular features of lung cancer in never-smokers. Eur Respir J. 2015;45(5):1403-14. https://doi.org/10.1183/09031936.00097214 PMid:25657019 DOI: https://doi.org/10.1183/09031936.00097214

Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers-a different disease. Nat Rev Cancer. 2007;7(10):778-90. https://doi.org/10.1038/nrc2190 PMid:17882278 DOI: https://doi.org/10.1038/nrc2190

McCarthy WJ, Meza R, Jeon J, Moolgavkar SH. Chapter 6: Lung cancer in never smokers: Epidemiology and risk prediction models. Risk Anal. 2012;32 Suppl 1:S69-84. https://doi.org/10.1111/j.1539-6924.2012.01768.x PMid:22882894 DOI: https://doi.org/10.1111/j.1539-6924.2012.01768.x

Torres-Duque C, Maldonado D, Pérez-Padilla R, Ezzati M, Viegi G, Forum of International Respiratory Studies (FIRS) Task Force on Health Effects of Biomass Exposure. Biomass fuels and respiratory diseases: A review of the evidence. Proc Am Thorac Soc. 2008;5(5):577-90. https://doi.org/10.1513/pats.200707-100RP PMid:18625750 DOI: https://doi.org/10.1513/pats.200707-100RP

Lim WY, Seow A. Biomass fuels and lung cancer. Respirology. 2012;17(1):20-31. https://doi.org/10.1111/j.1440-1843.2011.02088.x PMid:22008241 DOI: https://doi.org/10.1111/j.1440-1843.2011.02088.x

Park B, Kim Y, Lee J, Lee N, Jang SH. Sex difference and smoking effect of lung cancer incidence in asian population. Cancers (Basel). 2020;13(1):113. https://doi.org/10.3390/cancers13010113 PMid:33396462 DOI: https://doi.org/10.3390/cancers13010113

Gasperino J. Gender is a risk factor for lung cancer. Med Hypotheses. 2011;76(3):328-31. https://doi.org/10.1016/j.mehy.2010.10.030 PMid:21106301 DOI: https://doi.org/10.1016/j.mehy.2010.10.030

Freedman ND, Leitzmann MF, Hollenbeck AR, Schatzkin A, Abnet CC. Cigarette smoking and subsequent risk of lung cancer in men and women: Analysis of a prospective cohort study. Lancet Oncol. 2008;9(7):649-56. https://doi.org/10.1016/S1470-2045(08)70154-2 PMid:18556244 DOI: https://doi.org/10.1016/S1470-2045(08)70154-2

Liu T, Xie CB, Ma WJ, Chen WQ. Association between CYP2A6 genetic polymorphisms and lung cancer: A meta-analysis of case-control studies. Environ Mol Mutagen. 2013;54(2):133-40. https://doi.org/10.1002/em.21751 PMid:23203414 DOI: https://doi.org/10.1002/em.21751

Park SL, Murphy SE, Wilkens LR, Stram DO, Hecht SS, Le Marchand L. Association of CYP2A6 activity with lung cancer incidence in smokers: The multiethnic cohort study. PLoS One. 2017;12(5):e0178435. https://doi.org/10.1371/journal.pone.0178435 PMid:28542511 DOI: https://doi.org/10.1371/journal.pone.0178435

Benowitz NL, Swan GE, Jacob P 3rd, Lessov-Schlaggar CN, Tyndale RF. CYP2A6 genotype and the metabolism and disposition kinetics of nicotine. Clin Pharmacol Ther. 2006;80(5):457-67. https://doi.org/10.1016/j.clpt.2006.08.011 PMid:17112802 DOI: https://doi.org/10.1016/j.clpt.2006.08.011

Sepkovic DW, Haley NJ. Metabolism of Nicotine in Smokers and Nonsmokers. Boston, MA: Springer; 1987. p. 375-88. https://doi.org/10.1007/978-1-4613-1911-5_24 DOI: https://doi.org/10.1007/978-1-4613-1911-5_24

Kiyohara C, Takayama K, Nakanishi Y. CYP2A13, CYP2A6, and the risk of lung adenocarcinoma in a Japanese population. J Health Sci. 2005;51(6):658-66. https://doi.org/10.1248/jhs.51.658 DOI: https://doi.org/10.1248/jhs.51.658

Rossini A, de Almeida Simão T, Albano RM, Pinto LF. CYP2A6 polymorphisms and risk for tobacco-related cancers. Pharmacogenomics. 2008;9(11):1737-52. https://doi.org/10.2217/14622416.9.11.1737 PMid:19018727 DOI: https://doi.org/10.2217/14622416.9.11.1737

Soeroso NN, Zain-Hamid R, Sinaga BY, Sadewa AH, Syafiuddin T, Syahruddin E, et al. The Role of CYP2A6 genetic polymorphism in nicotine dependence and tobacco consumption among bataknese male smokers. Open Access Maced J Med Sci. 2018;6(5):864-6. https://doi.org/10.3889/oamjms.2018.224 PMid:29875862 DOI: https://doi.org/10.3889/oamjms.2018.224

Ariyoshi N, Miyamoto M, Umetsu Y, Kunitoh H, Dosaka-Akita H, Sawamura Y, et al. Cancer Epidemiology and Prevention Biomarkers; 2002. Available from: https://www.cebp.aacrjournals.org/content/11/9/890.long. [Last assecced on 2021 Mar 20].

Ma L, Jin G, Yang Y, Pang Y, Wang W, Zhang H, et al. Association between CYP2A13 polymorphisms and lung cancer. Medicine (Baltimore). 2020;99(50):e23289. https://doi.org/10.1097/md.0000000000023289 PMid:33327254 DOI: https://doi.org/10.1097/MD.0000000000023289

Timofeeva MN, Kropp S, Sauter W, Beckmann L, Rosenberger A, Illig T, et al. CYP450 polymorphisms as risk factors for early-onset lung cancer: Gender-specific differences. Carcinogenesis. 2009;30(7):1161-9. https://doi.org/10.1093/carcin/bgp102 PMid:19414505 DOI: https://doi.org/10.1093/carcin/bgp102

Zhang X, Su T, Zhang QY, Gu J, Caggana M, Li H, Ding X. Genetic polymorphisms of the human CYP2A13 gene: Identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant. J Pharmacol Exp Ther. 2002;302(2):416-23. https://doi.org/10.1124/jpet.302.2.416 PMid:2130698 DOI: https://doi.org/10.1124/jpet.302.2.416