Association of nasopharyngeal cancer risk with genetic polymorphisms of drug-metabolizing enzyme genes GSTM1, GSTT1 and CYP1A1 (rs4646903 variant), in tobacco addicted patients of Pashtun ethnicity of Khyber Pakhtunkhwa Province of Pakistan

Abstract

Associations of GSTM1, GSTT1 and CYP1A1 gene variants with risk of developing nasopharyngeal cancer were evaluated in this case-control study, in which 130 cases along with 151 population-based healthy controls of Pashtun ethnicity from Khyber Pakhtunkhwa province of Pakistan were recruited. Socio-demographic data were obtained and blood samples were collected with informed consent for analysis. Specific RT-PCR and conventional PCR methods were used to detect CYP1A1 and GSTs, respectively, and results analyzed through SPSS version 20. Study showed that CYP1A1 homozygous (C/C) had an almost 4-fold increased risk for nasopharyngeal cancer; while heterozygous (T/C) had an almost 2 times increased risk. Overall the C allele is sign ificantly associated with nasopharyngeal cancer as compared to T allele. Null genotypes of GSTM1 were having 3-fold increased risk; whereas null genotype of GSTT1 was having 2 times increased risk. Similarly, GSTM/GSTT both null genotype was having more than 5 times increased association. Presence of all three gene variants showed strong and significant association. Findings of the study suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 are significant risk factors for nasopharyngeal cancer susceptibility in Pashtun population