Interaction of Tobacco Smoking and Chewing with Angiotensin Converting Enzyme (Insertion/Deletion) Gene Polymorphisms and Risk of Lung Cancer in a High Risk Area from Northeast India

  • Published : 2015.01.22


Background: Association of angiotensin converting enzyme (ACE) gene polymorphisms with lung cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports an especially high rate of tobacco usage in a variety of ways of consumption, compared with the rest of the Indian population. Materials and Methods: We conducted a population based case control study in two major high risk region for lung cancer from Northeast India. A total of 151 consecutive lung cancer cases diagnosed histopathologically and equal numbers of controls were recruited with record of relevant sociodemographic information. Blood samples were collected and processed to identify ACE gene polymorphism. Results: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72; p=0.037) prevalence of the ACE II genotype was observed among lung cancer cases. Smoking was significantly associated with increased risk of lung cancer (OR=1.70, CI=1.02-2.81; p=0.041). An enhanced risk was also observed for interaction of ACE II genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) and chewing (OR=3.68, CI=1.22-11.13; p=0.021). Conclusions: The present study indicates significant association s of the ACE II genotype with lung cancer in high risk Northeast India.


Supported by : Indian Council of Medical Research


  1. Borah PK, Shankarishan P, Ahmed G, Mahanta J (2011). Polymorphism of angiotensin converting enzyme (insertion/deletion) and endothelial nitric oxide synthase (intron 4ab) genes in a population from north-east India. J Genet, 90, 105-9.
  2. Borah PK, Shankarishan P, Hazarika NC, Mahanta J (2012). Hypertension subtypes and angiotensin converting enzyme (ACE) gene polymorphism in Indian population. JAPI, 60, 11-7.
  3. Chaturvedi HK, Phukan RK, Mahanta J (2003). The association of selected socio-demographic factors and differences in pattern of substance use: a pilot study in selected areas of North-east India. Subst Use Misuse, 38, 1305-22.
  4. Cheon KT, Choi KH, Lee HB, et al (2000). Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with lung cancer. Lung, 178, 351-60.
  5. Chung CM, Wang RY, Fann CS, et al (2013). Fine-mapping angiotensin-converting enzyme gene: separate QTLs identified for hypertension and for ACE activity. PLoS One, 8, 56119.
  6. Correa SAA, Ribeiro-de-Noronha SM, Nogueira-de-Souza NC, et al (2009). Association between the angiotensin-converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms and breast cancer among Brazilian women. J Renin Angiotensin Aldosterone Syst, 10, 51-8.
  7. Devic PS, Ristic S, Flego V, Kapovic M, Radojcic BA (2012). Angiotensin-converting enzyme insertion/deletion gene polymorphism in lung cancer patients. Genet Test Mol Biomarkers, 16, 722-5.
  8. Drube S, Liebmann C (2000). In various tumour cell lines the peptide bradykinin B(2) receptor antagonist, Hoe 140 (Icatibant), may act as mitogenic agonist. Br J Pharmacol, 131, 1553-60.
  9. Freitas-Silva M, Pereira D, Coelho C, et al (2004). Angiotensin I-converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. Cancer Genet Cytogenet, 155, 42-6.
  10. Gard PR (2010). Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review. Int J Mol Epidemiol Genet, 1, 145-57.
  11. Goto Y, Ando T, Nishio K, et al (2005). The ACE gene polymorphism is associated with the incidence of gastric cancer among H. pylori seropositive subjects with atrophic gastritis. Asian Pac J Cancer Prev, 6, 464-7.
  12. Haiman CA, Henderson SO, Bretsky P, Kolonel LN, Henderson BE (2003). Genetic variation in angiotensin I-converting enzyme (ACE) and breast cancer risk: the multiethnic cohort. Cancer Res, 63, 6984-7.
  13. Keavney B, McKenzie CA, Connell JMC, et al (1998). Measured haplotype analysis of the angiotensin-I converting enzyme gene. Human Molecular Genetics, 7, 1745-51.
  14. Koh WP, Yuan JM, Sun CL, et al (2003). Angiotensin I-converting enzyme (ACE) gene polymorphism and breast cancer risk among Chinese women in Singapore. Cancer Res, 63, 573-8.
  15. Kramarenko II, Morinelli TA, Bunni MA, Raymond JRS, Garnovskaya MN (2012). The bradykinin B(2) receptor induces multiple cellular responses leading to the proliferation of human renal carcinoma cell lines. Cancer Manag Res, 4, 195-205.
  16. Kuoppala A, Lindstedt KA, Saarinen J, Kovanen PT, Kokkonen JO (2000). Inactivation of bradykinin by angiotensin-converting enzyme and by carboxypeptidase N in human plasma. Am J Physiol Heart Circ Physiol, 278, 1069-74.
  17. Li XL, Zheng ZJ, Qu HO (2014). Lack of association of angiotensin-converting enzyme insertion/deletion polymorphism with breast cancer: An update meta-analysis based on 10405 subjects. J Renin Angiotensin Aldosterone Syst, 2014, 1-6.
  18. Liu JF, Xie HJ, Cheng TM (2013). Lack of any association between insertion/deletion (I/D) polymorphisms in the angiotensin-converting enzyme gene and digestive system cancer risk: a meta-analysis. Asian Pac J Cancer Prev, 14, 7271-5.
  19. NCRP (2013). National cancer registry programme, three-year report of the population based cancer registries 2009-2011, (incidence and distribution of cancer: report of 25 PBCRs in India). Indian Council of Medical Research, Bangalore, India, pp 154-79.
  20. Nacak M, Nacak I, Sanli M, et al (2010). Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey. Cancer Genet Cytogenet, 198, 22-6.
  21. Pavlic SD, Ristic S, Flego V, Kapovic M, Badovinac AR (2012). Angiotensin-converting enzyme insertion/deletion gene polymorphism in lung cancer patients. Genetic Testing Molecular Biomarkers, 16, 722-5.
  22. Pei XH, HX Li (2012). Insertion/deletion (I/D) in the angiotensin-converting enzyme gene and breast cancer risk: lack of association in a meta- analysis. Asian Pac J Cancer Prev, 13, 5633-6.
  23. Phukan RK, Zomawia E, Narain K, Hazarika NC, Mahanta J (2005). Tobacco use and stomach cancer in Mizoram, India. Cancer Epidemiol Biomarkers Prev, 14, 1892-6.
  24. Phukan RK, Saikia BJ, Borah PK, et al (2014). Role of household exposure, dietary habits and glutathione S-transferases M1, T1 polymorphisms in susceptibility to lung cancer among women in Mizoram India. Asian Pac J Cancer Prev, 15, 3253-60.
  25. Sambrook J, Russel DW (2001). Purification of nucleic acid b extraction with phenol chloroform: in molecular cloning. cold spring harbor NY, US. Cold Spring Harbor Laboratory Press, 3, 8.
  26. Saikia BJ, Phukan RK, Sharma SK, Sekhon GS, Mahanta J (2014). Interaction of XRCC1 and XPD gene polymorphisms with lifestyle and environmental factors regarding susceptibility to lung cancer in a high incidence population in North East India. Asian Pac J Cancer Prev, 15, 1993-9.
  27. Shanmugam V, Sell KW, Saha BK (1993). Mistyping ACE heterozygotes. Genome Res, 3, 120-1.
  28. Sharma JD, Kalita M, Nirmolia T, et al (2014). Cancer: scenario and relationship of different geographical areas of the globe with special reference to North East-India. Asian Pac J Cancer Prev, 15, 3721-9.
  29. Vairaktaris E, Yapijakis C, Tsigris C, et al (2007). Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with increased risk for oral cancer. Acta Oncologica, 46, 1097-102.
  30. van der Knaap R, Siemes C, Coebergh JW, et al (2008). Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: the Rotterdam Study. Cancer, 112, 748-57.
  31. Yigit B, Bozkurt N, Narter F, et al (2007). Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis. Anticancer Res, 27, 933-6.
  32. Zhang Y, He J, Deng Y, et al (2011). The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis. BMC Med Genet, 12, 159.

Cited by

  1. gene polymorphisms and plasma nitric oxide with risk of non-small cell lung cancer in South India pp.17526981, 2016,
  2. Cost-effectiveness of lung cancer screening and treatment methods: a systematic review of systematic reviews vol.17, pp.1, 2017,
  3. Risk of major cancers associated with various forms of tobacco use in India: a systematic review and meta-analysis pp.1613-2238, 2018,