Association of CYP2A6 Genetic Polymorphism and Lung Cancer in Female Never Smokers

R.A Henny Anggriani, Noni Novisari Soeroso, Setia Putra Tarigan, Putri Chairani Eyanoer, Hidayat Hidayat


Background: The major significant factor that affected lung cancer development among female passive smokers is environmental tobacco smoke. Nicotine can be found in a never smoker population, such as a child whose father is a smoker. Lung carcinogenesis in never smoker populations is affected by nicotine metabolism by CYP2A6 gene, which encodes the main nicotine metabolizing-enzyme. The aim of this study was to assess the genetic polymorphism of CYP2A6 and its association with secondhand smokers among females who have suffered from lung cancer in North Sumatra population.

Materials and methods: This study was a case-control study, composed of 53 case subjects and 46 control subjects that were involved through a purposive sampling technique from two hospitals in Medan. PCR-RFLP was used for the examination of CYP2A6 gene to determine the genotype. The data were analyzed with conditional logistic regression test using Epi Info 7.0 software.

Results: The most common genotype of CYP2A6 detected in this study was *1B/*1B (40.4%), while *1B allele had the highest prevalence (55.5%). There was no significant association between CYP2A6 genotype (p-value=0.61) or alleles (p-value=0.25) and the incidence of lung cancer.

Conclusion: There was no association between CYP2A6 polymorphism and the incidence of lung cancer in secondhand smoker females.

Keywords: CYP2A6, PCR-RFLP, female secondhand smokers, lung cancer

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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, CrossRef.

Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: Epidemiology, etiology, and prevention. Clin Chest Med. 2011; 32(4): 605-44, CrossRef.

Kim CH, Lee YC, Hung RJ, McNallan SR, Cote ML, Lim WY, et al. Exposure to secondhand tobacco smoke and lung cancer by histological type: A pooled analysis of the International Lung Cancer Consortium (ILCCO). Int J Cancer. 2014; 135(8):1918–30, CrossRef.

Toh CK, Gao F, Lim WT, Leong SS, Fong KW, Yap SP, et al. Never-smokers with lung cancer: Epidemiologic evidence of a distinct disease entity. J Clin Oncol. 2006; 24(15): 2245–51, CrossRef.

Brambilla E, Gazdar A. Pathogenesis of lung cancer signalling pathways: Roadmap for therapies. Eur Respir J. 2009; 33(6): 1485–97, CrossRef.

Ezzeldin N, El-Lebedy D, Darwish A, El Bastawisy A, Abd Elaziz SH, Hassan MM, et al. Association of genetic polymorphisms CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 with tobacco-induced lung cancer: Case-control study in an Egyptian population. BMC Cancer. 2018; 18(1): 525, CrossRef.

Tan W, Chen GF, Xing DY, Song CY, Kadlubar FF, Lin DX. Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer. 2001; 95(2): 96–101, CrossRef.

Yoshida R, Nakajima M, Watanabe Y, Kwon JT, Yokoi T. Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Br J Clin Pharmacol. 2002; 54(5): 511–7, CrossRef.

Rao Y, Hoffmann E, Zia M, Bodin L, Zeman M, Sellers EM, et al. Duplications and defects in the CYP2A6 gene: Identification, genotyping, and in vivo effects on smoking. Mol Pharmacol. 2000; 58(4): 747–55, CrossRef.

Patramurti C, Sugiyanto, Nurrochmad A, Martono S. Polymorphism of cytochrome P450 2A6 (CYP2A6*1 and CYP2A6*4) among Javanese Indonesian smoker and non smoker. Indonesian J Pharm. 2015; 26(1): 11-19, CrossRef.

Soeroso NN, Zain-Hamid R, Sinaga BYM, 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, CrossRef.

Soeroso NN, Ananda FR. Lung cancer among never-smoker women: An epidemiological data in North Sumatera, Indonesia. Int J Respir Med. 2019; 1(1): 1-9, article.

Torres-Duque C, Maldonado D, Pérez-Padilla R, Ezzati M, Viegi G. Biomass fuels and respiratory diseases: A review of the evidence. Proc Am Thorac Soc. 2008; 5(5): 577–90, CrossRef.

Lim WY, Seow A. Biomass fuels and lung cancer. Respirology. 2012; 17(1): 20–31, CrossRef.

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, CrossRef.

Gasperino J. Gender is a risk factor for lung cancer. Med Hypotheses. 2011; 76(3): 328–31, CrossRef.

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, CrossRef.

Mong C, Garon EB, Fuller C, Mahtabifard A, Mirocha J, Mosenifar Z, et al. High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation. J Cardiothorac Surg. 2011; 6: 19, CrossRef.


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