The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers


Genetic polymorphisms of genes whose products are responsible for activities, such as xenobiotic metabolism, mutagen detoxification and DNA-repair, have been predicted to be associated with the risk of developing lung cancer (LC). The association of LC with tobacco smoking has been extensively investigated, but no studies have focused on the Arab ethnicity. Previously, we examined the association between genetic polymorphisms among Phase I and Phase II metabolism genes and the risk of LC. Here, we extend the data by examining the correlation of OGG1 Ser326Cys combined with CYP1A1 (Ile462Val and MspI) and GSTP1 (Ile105Val and Ala103Val) polymorphisms with the risk of LC. Polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and gene sequencing were carried out for genotyping the OGG1 polymorphisms of 123 LC patients and 129 controls. No significant differences in the frequencies of the OGG1 mutant allele between patients and controls were found. The distributions of heterozygous Ser/Cys or Cys/Cys genotypes of OGG1 were not associated with the risk of LC either according to the histological types of LC or based on waterpipe tobacco (WP) smoking status. In contrast, the combined effect of OGG1 variants with CYP1A1 and GSTP1 variants revealed a significant correlation with the OGG1 Ser326Cys—CYP1A1 MspI variants pairing. This association was significant (p = 0.001) in individuals who carried homozygous or heterozygous variant type genotypes of both genes in a reference with carriers of both wild-type genotypes (wt/wt − wt/wt). The odds ratios were 2.99 (95% CI 1.67–5.36), 2.68 (95% CI 1.08–6.62), and 2.80 (95% CI 1.18–6.69) for those who carried (wt/wt − wt/vt + vt/vt), (wt/vt + vt/vt − wt/wt), and (wt/vt + vt/vt − wt/vt + vt/vt), respectively. The study suggests a limited correlation is present between carrying OGG1 Ser326Cys polymorphism and the risk of developing LC in Arab populations.

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  1. 1.

    Adcock IM, Caramori G, Barnes PJ (2011) Chronic obstructive pulmonary disease and lung cancer: new molecular insights. Respiration 81(4):265–284

    CAS  PubMed  Google Scholar 

  2. 2.

    Møller P et al (2008) Air pollution, oxidative damage to DNA, and carcinogenesis. Cancer Lett 266(1):84–97

    PubMed  Google Scholar 

  3. 3.

    Cobb CO, Shihadeh A, Weaver MF, Eissenberg T (2011) Waterpipe tobacco smoking and cigarette smoking: a direct comparison of toxicant exposure and subjective effects. Nicotine Tobacco Res 13(2):78–87

    CAS  Google Scholar 

  4. 4.

    Shihadeh A, Schubert J, Klaiany J, El Sabban M, Luch A, Saliba NA (2015) Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives. Tobacco Control 24(Suppl 1):i22–i30

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Ateş A, Arikan M, Özgök A (2016) An unusual cause of carbon monoxide poisoning: narghile smoking. Am J Case Rep 17:660–662

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Monzer B, Sepetdjian E, Saliba N, Shihadeh A (2008) Charcoal emissions as a source of CO and carcinogenic PAH in mainstream narghile waterpipe smoke. Food Chem Toxicol 46(9):2991–2995

    CAS  PubMed  Google Scholar 

  7. 7.

    DeMarini DM et al (2001) Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions. Can Res 61(18):6679–6681

    CAS  Google Scholar 

  8. 8.

    Daher N et al (2010) Comparison of carcinogen, carbon monoxide, and ultrafine particle emissions from narghile waterpipe and cigarette smoking: Sidestream smoke measurements and assessment of second-hand smoke emission factors. Atmos Environ (Oxford, England: 1994) 44(1):8–14

    CAS  Google Scholar 

  9. 9.

    El-Nachef WN, Hammond SK (2008) Exhaled carbon monoxide with waterpipe use in US students. JAMA 299(1):36–38

    CAS  PubMed  Google Scholar 

  10. 10.

    Shihadeh A et al (2012) Does switching to a tobacco-free waterpipe product reduce toxicant intake? A crossover study comparing CO, NO, PAH, volatile aldehydes, ‘tar’ and nicotine yields. Food Chem Toxicol 50(5):1494–1498

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Fearon ER (1997) Human cancer syndromes: clues to the origin and nature of cancer. Science (New York, N.Y.) 278(5340):1043–1050

    CAS  Google Scholar 

  12. 12.

    Marnett LJ (2000) Oxyradicals and DNA damage. Carcinogenesis 21(3):361–370

    CAS  Google Scholar 

  13. 13.

    Deng N, Zhou H, Fan H, Yuan Y (2017) Single nucleotide polymorphisms and cancer susceptibility. Oncotarget 8(66):110635–110649

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Bhattacharya R, Rose PW, Burley SK, Prlić A (2017) Impact of genetic variation on three dimensional structure and function of proteins. PLoS ONE 12(3):e0171355

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Yarden Y (2001) The EGFR family and its ligands in human cancer. Eur J Cancer 37:3–8

    Google Scholar 

  16. 16.

    Fan H et al (2010) A functional polymorphism in the DNA methyltransferase-3A promoter modifies the susceptibility in gastric cancer but not in esophageal carcinoma. BMC Med 8(1):12

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Rintisch C et al (2014) Natural variation of histone modification and its impact on gene expression in the rat genome. Genome Res 24(6):942–953

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Wu H et al (2014) A novel functional TagSNP Rs7560488 in the DNMT3A1 promoter is associated with susceptibility to gastric cancer by modulating promoter activity. PLoS ONE 9(3):-e92911

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Pagenstecher C et al (2006) Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants. Hum Genet 119(1–2):9–22

    CAS  PubMed  Google Scholar 

  20. 20.

    Fang W et al (2014) The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: case-control and a meta-analysis. Mutat Res 770:61–68

    CAS  PubMed  Google Scholar 

  21. 21.

    Dunna NR et al (2014) Association of thymidylate synthase 5’-UTR 28bp tandem repeat and serine hydroxymethyltransfarase C1420T polymorphisms with susceptibility to acute leukemia. Asian Pac J Cancer Prev APJCP 15(4):1719–1723

    PubMed  Google Scholar 

  22. 22.

    Xu Q et al (2014) The interaction effects of pri-let-7a-1 rs10739971 with PGC and ERCC6 gene polymorphisms in gastric cancer and atrophic gastritis. PLoS ONE 9(2):e89203

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Scott TL, Rangaswamy S, Wicker CA, Izumi T (2014) Repair of oxidative DNA damage and cancer: recent progress in DNA base excision repair. Antioxid Redox Signal 20(4):708–726

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Arai K et al (1997) Cloning of a human homolog of the yeast OGG1 gene that is involved in the repair of oxidative DNA damage. Oncogene 14(23):2857–2861

    CAS  PubMed  Google Scholar 

  25. 25.

    Lai C-Y, Hsieh L-L, Tang R, Santella RM, Chang-Chieh CR, Yeh C-C (2016) Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan. World J Gastroenterol 22(12):3372–3380

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Audebert M, Radicella JP, Dizdaroglu M (2000) Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein. Nucleic Acids Res 28(14):2672–2678

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Xu J et al (2002) Associations between hOGG1 sequence variants and prostate cancer susceptibility. Can Res 62(8):2253–2257

    CAS  Google Scholar 

  28. 28.

    Habib SL et al (2008) Genetic polymorphisms in OGG1 and their association with angiomyolipoma, a benign kidney tumor in patients with tuberous sclerosis. Cancer Biol Ther 7(1):23–27

    CAS  PubMed  Google Scholar 

  29. 29.

    Kershaw RM, Hodges NJ (2012) Repair of oxidative DNA damage is delayed in the Ser326Cys polymorphic variant of the base excision repair protein OGG1. Mutagenesis 27(4):501–510

    CAS  PubMed  Google Scholar 

  30. 30.

    Duan W-X et al (2012) The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies. PLoS ONE 7(4):e35970

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Yu T et al (2018) Rs3212986 polymorphism, a possible biomarker to predict smoking-related lung cancer, alters DNA repair capacity via regulating ERCC1 expression. Cancer Med 7(12):6317–6330

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Mitra AK, Singh SV, Garg VK, Sharma M, Chaturvedi R, Rath SK (2011) Protective association exhibited by the single nucleotide polymorphism (SNP) rs1052133 in the gene human 8-oxoguanine DNA glycosylase (hOGG1) with the risk of squamous cell carcinomas of the head & neck (SCCHN) among north Indians. Indian J Med Res 133(6):605–612

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Ramsey AT et al (2020) Low burden strategies are needed to reduce smoking in rural healthcare settings: a lesson from cancer clinics. Int J Environ Res Public Health 17(5):1728

    PubMed Central  Google Scholar 

  34. 34.

    Kudhair BK, Lafta IJ, Alabid NN (2020) Waterpipe tobacco smoking and gene variants of CYP1A1-Ile462Val and -MspI polymorphisms are possibly associated with the risk of lung cancer in the Iraqi population. Meta Gene 23(October 2019):100623

    Google Scholar 

  35. 35.

    Kudhair BK, Alabid NN, Taheri-Kafrani A, Lafta IJ (2020) Correlation of GSTP1 gene variants of male Iraqi waterpipe (Hookah) tobacco smokers and the risk of lung cancer. Mol Biol Rep 47(4):2677–2684

    CAS  PubMed  Google Scholar 

  36. 36.

    Kohno T et al (1998) Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene 16(25):3219–3225

    CAS  PubMed  Google Scholar 

  37. 37.

    Sugimura H et al (1999) hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomark Prev 8(8):669–674

    CAS  Google Scholar 

  38. 38.

    Le Marchand L, Donlon T, Lum-Jones A, Seifried A, Wilkens LR (2002) Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk. Cancer Epidemiol Biomark Prev 11(4):409–412

    Google Scholar 

  39. 39.

    Park J, Chen L, Tockman MS, Elahi A, Lazarus P (2004) The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk. Pharmacogenetics 14(2):103–109

    CAS  PubMed  Google Scholar 

  40. 40.

    Loft S et al (2006) Prospective study of 8-oxo-7,8-dihydro-2’-deoxyguanosine excretion and the risk of lung cancer. Carcinogenesis 27(6):1245–1250

    CAS  PubMed  Google Scholar 

  41. 41.

    Li H, Hao X, Zhang W, Wei Q, Chen K (2008) The hOGG1 Ser326Cys polymorphism and lung cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 17(7):1739–1745

    Google Scholar 

  42. 42.

    Ito H et al (2002) A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung. J Epidemiol 12(3):258–265

    PubMed  Google Scholar 

  43. 43.

    Liang G, Pu Y, Yin L (2005) Rapid detection of single nucleotide polymorphisms related with lung cancer susceptibility of Chinese population. Cancer Lett 223(2):265–274

    CAS  PubMed  Google Scholar 

  44. 44.

    Wei Q, Cheng L, Hong WK, Spitz MR (1996) Reduced DNA repair capacity in lung cancer patients. Can Res 56(18):4103–4107

    CAS  Google Scholar 

  45. 45.

    Klinchid J, Chewaskulyoung B, Saeteng S, Lertprasertsuke N, Kasinrerk W, Cressey R (2009) Effect of combined genetic polymorphisms on lung cancer risk in northern Thai women. Cancer Genet Cytogenet 195(2):143–149

    CAS  PubMed  Google Scholar 

  46. 46.

    Chan BA, Hughes BGM (2015) Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res 4(1):36–54

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Jurišić V, Obradovic J, Pavlović S, Djordjevic N (2018) Epidermal growth factor receptor gene in non-small-cell lung cancer: the importance of promoter polymorphism investigation. Anal Cell Pathol 2018:1–9

    Google Scholar 

  48. 48.

    Elez-Burnjakovic N et al (2018) Distribution of EGFR SNPs -191C/A and 181946G/A in patients with lung cancer depending on smoking status in the Republic of Srpska Bosnia and Herzegovina. J BUON 23(2):384–390

    PubMed  Google Scholar 

  49. 49.

    Stumbryte A, Gudleviciene Z, Kundrotas G, Dabkeviciene D, Kunickaite A, Cicenas S (2018) Individual and combined effect of TP53, MDM2, MDM4, MTHFR, CCR5, and CASP8 gene polymorphisms in lung cancer. Oncotarget 9(3):3214–3229

    PubMed  Google Scholar 

  50. 50.

    AlReza H, Anamika WJ, Chowdhury MMK, Mostafa MG, Uddin MA (2020) A cohort study on the association of MDM2 SNP309 with lung cancer risk in Bangladeshi population. Korean J Internal Med 35(3):672–681

    Google Scholar 

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The authors would like to thank Dr. Joseph Webb, the University of Sheffield at the department of Molecular Biology and Biotechnology and Dr. Mohammed Jawad, Imperial College London at the Faculty of Medicine, School of Public Health for reviewing, carefully revising, and proofreading of this paper.


This study was funded by laboratory investigations department, University of Kufa; (Project Grant BKK00587).

Author information




B.K.K., N.N.A., and K.S.A., carried out the experiments and analyzed data. N.N.A. also contributed by doing the statistical analysis. B.K.K conceived the study, supervised the experiments, and wrote the manuscript. I.J.L and A.T-K provided extra supervision.

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Correspondence to Bassam K. Kudhair.

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Kudhair, B.K., Alabid, N.N., Zayed, K.S. et al. The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers. Mol Biol Rep (2020).

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  • Lung cancer
  • 8-oxoguanine DNA glycosylase
  • OGG1
  • rs1052133
  • CYP1A1
  • GSTP1
  • Waterpipe tobacco