The Effect of CHRNA3 Rs1051730 C>T and ABCB1 Rs3842 A>G Polymorphisms on Non-small Cell Lung Cancer and Nicotine Dependence in Iranian Population

Overview

Journal Heliyon

Specialty Social Sciences

Date 2021 Sep 15

PMID 34522797

Citations 1

Authors

Parisa Veiskarami

Massoud Houshmand

Sharareh Seifi

Nafiseh Ansarinejad

Farshid Fardad

Bahareh Abbasi

Affiliations

Soon will be listed here.

Abstract

Aims: Lung cancer is still the leading cause of cancer mortality in all over the world. Nicotine and its derivatives are the most well-known carcinogens that participate in both etiology and progression of lung cancer. The objective of the current study was to investigate whether single nucleotide polymorphisms (SNPs) rs1051730C > T in CHRNA3 and rs3842A > G in ABCB1, two genes contributing in the mechanism of disposition and metabolism of nicotine and its derivatives, could modify the risk of developing lung cancer, as well as nicotine dependence in Iranian.

Main Methods: The genotyping analysis for these two SNPs was conducted in a case-control study of 108 lung cancer cases and 120 healthy controls using ARMS-PCR and Tetra-primer ARMS-PCR techniques. The correlation between studied SNPs and lung cancer was assessed by the regression analysis.

Key Findings: We observed a significant association between lung cancer and rs1051730C > T by using four genetic models: allele (OR:1.83; 95% CI:1.24-2.6; p = 0.002), dominant (OR: 2.19; 95% CI:1.27-3.78; p = 0.005), recessive (OR: 2.25; 95% CI: 1.02-4.95; p = 0.043) and additive (TT vs CC: OR:3.25; 95% CI:1.38-7.60; p = 0.007, CT vs CC: OR:1.96; 95% CI:1.10-3.48; p = 0.021). Furthermore, a significant association between this variant and nicotine dependence (OR: 2.27; 95% CI: 1.52-3.39; p = 0.00005) was reported. However, no association was found for rs3842A > G.

Significance: The results suggested that the CHRNA3 rs1051730C > T via a smoking-dependent manner could modify susceptibility to lung cancer among Iranian population.

Citing Articles

Genetic analysis of suicide: a sample study in Tuscany (Central Italy).

Focardi M, Gualco B, Pinchi V, Gian-Aristide N, Rensi R, Pelo E Forensic Sci Res. 2023; 7(4):790-797.

PMID: 36817247 PMC: 9930793. DOI: 10.1080/20961790.2020.1835156.

References

Hodges L, Markova S, Chinn L, Gow J, Kroetz D, Klein T . Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet Genomics. 2010; 21(3):152-61. PMC: 3098758. DOI: 10.1097/FPC.0b013e3283385a1c. View

Han Z, Jiang Q, Zhang T, Wu X, Ma R, Wang J . Analyzing large-scale samples confirms the association between the rs1051730 polymorphism and lung cancer susceptibility. Sci Rep. 2015; 5:15642. PMC: 4623668. DOI: 10.1038/srep15642. View

Scheffer G, Pijnenborg A, Smit E, Muller M, Postma D, Timens W . Multidrug resistance related molecules in human and murine lung. J Clin Pathol. 2002; 55(5):332-9. PMC: 1769658. DOI: 10.1136/jcp.55.5.332. View

Shiraishi K, Kohno T, Kunitoh H, Watanabe S, Goto K, Nishiwaki Y . Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese. Carcinogenesis. 2008; 30(1):65-70. DOI: 10.1093/carcin/bgn257. View

Kupiainen H, Kuokkanen M, Kontto J, Virtamo J, Salomaa V, Lindqvist A . CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers. COPD. 2016; 13(4):464-70. DOI: 10.3109/15412555.2015.1049260. View

Wang H, Jin G, Wang H, Liu G, Qian J, Jin L . Genetic susceptibility of lung cancer associated with common variants in the 3' untranslated regions of the adenosine triphosphate-binding cassette B1 (ABCB1) and ABCC1 candidate transporter genes for carcinogen export. Cancer. 2008; 115(3):595-607. DOI: 10.1002/cncr.24042. View

Thorgeirsson T, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson K . A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature. 2008; 452(7187):638-642. PMC: 4539558. DOI: 10.1038/nature06846. View

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

Hu B, Huang Y, Yu R, Mao H, Guan C, Zhao J . Quantitative assessment of the influence of common variations (rs8034191 and rs1051730) at 15q25 and lung cancer risk. Tumour Biol. 2013; 35(3):2777-85. DOI: 10.1007/s13277-013-1369-8. View

10.

Li H, Yang L, Zhao X, Wang J, Qian J, Chen H . Prediction of lung cancer risk in a Chinese population using a multifactorial genetic model. BMC Med Genet. 2012; 13:118. PMC: 3573944. DOI: 10.1186/1471-2350-13-118. View

11.

Ji X, Bosse Y, Landi M, Gui J, Xiao X, Qian D . Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk. Nat Commun. 2018; 9(1):3221. PMC: 6089967. DOI: 10.1038/s41467-018-05074-y. View

12.

Shou W, Wang D, Zhang K, Wang B, Wang Z, Shi J . Gene-wide characterization of common quantitative trait loci for ABCB1 mRNA expression in normal liver tissues in the Chinese population. PLoS One. 2012; 7(9):e46295. PMC: 3458811. DOI: 10.1371/journal.pone.0046295. View

13.

Stadler Z, Thom P, Robson M, Weitzel J, Kauff N, Hurley K . Genome-wide association studies of cancer. J Clin Oncol. 2010; 28(27):4255-67. PMC: 2953976. DOI: 10.1200/JCO.2009.25.7816. View

14.

Wu C, Hu Z, Yu D, Huang L, Jin G, Liang J . Genetic variants on chromosome 15q25 associated with lung cancer risk in Chinese populations. Cancer Res. 2009; 69(12):5065-72. DOI: 10.1158/0008-5472.CAN-09-0081. View

15.

Yang L, Qiu F, Lu X, Huang D, Ma G, Guo Y . Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese. PLoS One. 2012; 7(10):e46071. PMC: 3463594. DOI: 10.1371/journal.pone.0046071. View

16.

Timofeeva M, Hung R, Rafnar T, Christiani D, Field J, Bickeboller H . Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls. Hum Mol Genet. 2012; 21(22):4980-95. PMC: 3607485. DOI: 10.1093/hmg/dds334. View

17.

Wen L, Jiang K, Yuan W, Cui W, Li M . Contribution of Variants in CHRNA5/A3/B4 Gene Cluster on Chromosome 15 to Tobacco Smoking: From Genetic Association to Mechanism. Mol Neurobiol. 2014; 53(1):472-484. DOI: 10.1007/s12035-014-8997-x. View

18.

Kita-Milczarska K, Sieminska A, Jassem E . Association Between CHRNA3 and CHRNA5 Nicotine Receptor Subunit Gene Variants and Nicotine Dependence in an Isolated Populationof Kashubians in Poland. Med Sci Monit. 2016; 22:1442-50. PMC: 4915318. DOI: 10.12659/msm.895907. View

19.

Sun H, Pan Y, He B, Deng Q, Ying H, Chen J . Different effects of the three polymorphisms on 15q25.1 onlung cancer risk: Evidence from published literatures. J Cancer Res Ther. 2016; 12(1):12-9. DOI: 10.4103/0973-1482.151863. View

20.

Gu M, Dong X, Zhang X, Wang X, Qi Y, Yu J . Strong association between two polymorphisms on 15q25.1 and lung cancer risk: a meta-analysis. PLoS One. 2012; 7(6):e37970. PMC: 3368941. DOI: 10.1371/journal.pone.0037970. View