Abstract
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.
Highlights
Oral cancer is the fourth most common cancer in the world (Amtha et al, 2009; Gupta and Johnson, 2014)
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
Present data shows that genetic polymorphisms in GSTM1, GSTT1 and CYP1A1 genes have important contribution towards the occurrence of oral cancer in Pashtun population
Summary
Oral cancer is the fourth most common cancer in the world (Amtha et al, 2009; Gupta and Johnson, 2014). Some studies have shown the association of polymorphisms in CYP1A1 and GSTM1 genes with oral cancer (Tanimoto et al, 1999; Wogan et al, 2004), while some studies have reported a lack of association (Park et al, 2000; Olshan et al, 2000; Sreelekha et al, 2001; Sharma et al, 2006; Cha et al, 2007) These seemingly conflicting observations are due to geographic and ethnic variations in the distribution of genotype frequencies of both CYP and GST alleles along with other environmental factors. A case-control study was carried out to evaluate the potential role of CYP1A1 (T>C, rs4646903), GSTM1 and GSTT1 gene polymorphisms in the susceptibility to oral cancer in Pashtun population of Khyber Pakhtunkhwa province of Pakistan This will help to adopt pro-active approaches for early detection and preventive life style modification strategies to decrease the incidence of the disease in the target population
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