Genetic Susceptibility to Oral Cancer due to Combined Effects of GSTT1, GSTM1 and CYP1A1 Gene Variants in Tobacco Addicted Patients of Pashtun Ethnicity of Khyber Pakhtunkhwa Province of Pakistan

  • Published : 2015.03.04


Associations of GSTT1, GSTM1 and CYP1A1 gene variants with risk of developing oral cancer were evaluated in this study. A case-control study was conducted in Pashtun population of Khyber Pakhtunkhwa province of Pakistan in which 200 hospital based oral cancer cases and 151 population based healthy controls exposed to similar environmental conditions were included. Sociodemographic data were obtained and blood samples were collected with informed consent for analysis. GSTM1 and GSTT1 were analysed through conventional PCR method while specific RT-PCR method was used to detect CYP1A1 polymorphisms. Results were analyzed for conditional logistic regression model by SPSS version 20. The study shows that patients with either GSTM1 or GSTT1 null genotypes have significantly higher risk of oral cancer (adjusted odds (OR): (3.019 (1.861-4.898) and 3.011(1.865-4.862), respectively), which further increased when either one or both null genes were present in combination (adjusted odds (OR): (3.627 (1.981-6.642 and 9.261 (4.495-19.079), respectively). CYP1A1 rs4646903 gene variants individually showed weak association OR: 1.121 (0.717-1.752); however, in the presence of GSTM1 and/or GSTT1 null genotypes further increasing the association (adjusted odds (ORs): 4.576 (2.038-10.273), 5.593 (2.530-12.362) and 16.10 (3.854-67.260 for GSTM/GSTT null and CYP1A1 wild type, GSTM/GSTT either null and CYP1A1 variant alleles, and all 3 gene polymorphisms combinations, respectively). Our findings suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 may be the risk alleles for oral cancer susceptibility in Pashtun population.


  1. Abbas M, Srivastava K, Imran M, Banerjee M (2014). Association of CYP1A1 gene variants rs4646903 (T>C) and rs1048943 (A>G) with cervical cancer in a North Indian population. Eur J Obstet Gynecol Reprod Biol, 176, 68-74.
  2. Amtha R, Ching CS, Zain R, et al (2009). GSTM1, GSTT1 and CYP1A1 polymorphisms and risk of oral cancer: a casecontrol study in Jakarta, Indonesia. Asian Pacific J Cancer Prev, 10, 21-26.
  3. Ariyawardana A, Johnson NW (2013). Trends of lip, oral cavity and oropharyngeal cancers in Australia 1982-2008: overall good news but with rising rates in the oropharynx. BMC Cancer, 13, 333.
  4. Balaram P, Sridhar H, Rajkumar T et al (2002). Oral cancer in southern India: the influence of smoking, drinking, paanchewing and oral hygiene. Int J Cancer, 98, 440-5.
  5. Bhurgri Y, Bhurgri A, Nishter S, et al (2006). Pakistan - country profile of cancer and cancer control 1995-2004. J Pak Med Assoc, 56, 124-30.
  6. Bile KM, Shaikh JA, Afridi HU, Khan Y (2010). Smokeless tobacco use in Pakistan and its association with oropharyngeal cancer. East Mediterr Health J, 16, 24-30.
  7. Cha In-Ho, Park JY, Chung WY, et al (2007). Polymorphisms of CYP1A1 and GSTM1 genes and susceptibility to oral cancer. Yonsei Med J, 48, 233-9.
  8. D'Errico A, Taioli E, Xhen X, et al (1996). Genetic metabolic polymorphisms and the risk of cancer: a review of the literature. Biomark, 1, 149-73.
  9. Dikshit RP, Kanhere S (2000). Tobacco habits and risk of lung, oropharyngeal and oral cavity cancer: a population- based case-control study in Bhopal, India. Int J Epidemiol, 29, 609-14.
  10. Gupta B, Johnson NW (2014). Emerging and established global life-style risk factors for cancer of the upper aero-digestive tract. Asian Pac J Cancer Prev, 15, 5983-91.
  11. Hirschhorn JN, Lohmueller K, Byrne E, (2002). A comprehensive review of genetic association studies. Genet Med, 4, 45-61.
  12. Masood N, Yasmin A, Kayani MA, (2013). Genetic deletions of GSTM1 and GSTT1 in head and neck cancer: review of the literature from 2000 to 2012. Asian Pac J Cancer Prev, 14, 3535-9.
  13. Merchant A, Husain SS, Hosain M et al (2000). Paan without tobacco: an independent risk factor for oral cancer. Int J Cancer, 86, 128-31.<128::AID-IJC20>3.0.CO;2-M
  14. Moore SR, Johnson NW, Pierce AM, Wilson DF (2000). The epidemiology of mouth cancer: a review of global incidence. Oral Dis, 6, 65-74.
  15. Nair UJ, Nair J, Mathew B, Bartsch M (1999). Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers. Carcinogenesis, 20, 743-48.
  16. Nandakumar A, Thimmasetty KT, Sreeramareddy NM et al (1990). A population-based case-control investigation on cancers of the oral cavity in Bangalore, India. Br J Cancer, 62, 847-51.
  17. Olshan AF, Weissler MC, Bell DA (2000). GSTM1, GSTT1, GSTP1, CYP1A1, and NAT1 polymorphisms, tobacco use, and the risk of head and neck cancer. Cancer Epidemiol Biomark Prev, 9, 185-91.
  18. Park JY, Muscat JE, Kaur T, et al (2000). Comparison of GSTM polymorphisms and risk of oral cancer between African- American and Caucasians. Pharmacogenetics, 10, 123-31.
  19. Prokopczyk B, Cox JE, Hoffmann D, et al (1997). Identification of tobacco specific carcinogen in the cervical mucus of smokers and non-smokers. J Natl Cancer Inst, 89, 868-73.
  20. Rao DN, Desai PB (1998). Risk assessment of tobacco, alcohol and diet in cancers of base tongue and oral tongue-a case control study. Indian J Cancer, 35, 65-72.
  21. Rickert WS, Joza PJ, Trivedi AH et al (2009). Chemical and toxicological characterization of commercial smokeless tobacco products available on the canadian market. Regul Toxicol Pharmaco, 53, 121-33.
  22. Sabitha K, Reddy MV, Jamil K (2010). Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer. Cancer Epidemiol, 34, 587-92.
  23. Sharma A, Mishra A, Das BC, Sardana S, Sharma JK (2006). Genetic polymorphism at GSTM1 and GSTT1 gene loci and susceptibility to oral cancer. Neoplasma, 53, 309-15.
  24. Sreelekha TT, Ramadas K, Pandey M, et al (2001). Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer. Oral Oncol, 37, 593-8.
  25. Tanimoto K, Hayashi S, Yoshiga K, Ichikawa T (1999). Polymorphisms of the CYP 1A1 and GSTM1 gene involved in oral squamous cell carcinoma in association with a cigarette dose. Oral Oncol, 35, 191-6.
  26. Velema JP, Ferrera A, Figueroa M, et al (2002). Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras. Int J Cancer, 97, 536-41.
  27. Warnakulasuriya S, Sutherland G, Scully C (2005). Tobacco, oral cancer, and treatment of dependence. Oral Oncol, 41, 244-60.
  28. Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA (2004). Environmental and chemical carcinogenesis. Semin Cancer Biol, 14, 473-86.
  29. Xia L, Gao J, Liu Y, et al (2013). Significant association between CYP1A1 T3801C polymorphism and cervical neoplasia risk: a systematic review and meta-analysis. Tumor Biol, 34, 223-30.
  30. Znaor A, Brennan P, Gajalakshmi V et al (2003). Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer, 105, 681-6.
  31. Zakiullah, Saeed M, Ali S et al (2014). Genetic susceptibility to esophageal cancer due to CYP1A1 gene variant rs4646903 in tobacco addicted patients of Pashtun ethnicity: a case control study in Khyber Pakhtunkhwa province of Pakistan. Asian Pac J Cancer Prev, 15, 6715-20.

Cited by

  1. Preliminary Study of the GSTM1 Null Polymorphism and History of Tobacco Smoking among Oral Cancer Patients in Northeastern Thailand vol.17, pp.2, 2016,