Public Defense of a Ph.D Research Scholar at Department of Pharmacy
- 10:00 am
- Department of Pharmacy, UoP
CYP1A1, GSTM1 and GSTT1 are major xenobiotic metabolizing enzymes involved in processing of various tobacco related carcinogens. Polymorphisms in genes related to these enzymes have frequently been associated with increased incidence of different type of cancers that follow diverse patterns in different types of populations.The purpose of this study was to evaluate the associations of CYP1A1, GSTM1 and GSTT1 gene variants with the risk of developing oral, pharyngeal, and esophageal and Non- Hodgkin's Lymphoma (NHL) cancers in tbbacco addicted individuals of Pashtun ethnicity of Khyber Pakhtunkhwa province. A case-control study was conducted in 200 hospital based oral, 130 pharyngeal, 140 esophageal cancer cases, and 183 NHL cases along with 151 (each) population based healthy controls exposed to similar environmental conditions. Socio-demographic data were obtained and blood samples collected with informed consent for analysis. GSTM1 and GSTT1 were analysed through conventional PCR method while specific RT-PCRmethod was used to detect CYP1A1 polymorphisms. Results were analyzed for conditional logistic regression model by SPSS version 20.
Results for different cancers were as follows:
Oral cancer: GSTM1 or GSTT1 null genotypes have significantly higher risk of oral cancer (OR): (3.019 (1.861-4.898) and 3.011(1.865-4.862; p-value = 0.000), respectively). CYP1A1 rs4646903 gene variants in the presence of GSTM1 and/or GSTT1 null genotypes further increasing the association. Findings of the research 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.
Pharyngeal cancer: CYP1A1 homozygous variant type (C/C) had an almost 4- fold increased risk for pharyngeal cancer (T/T) (OR: 3.810 (1.505-9.640), p-value=0.005); while heterozygous variant (T/C) had an almost 2 times increased risk for oral cancer (T/T) (OR: 1.701 (1.055-2 743) ^-value = 0.029) at 95% CI. Overall the C allele is significantly associated with the occurrence of pharyngeal cancer .Null genotypes of GSTM1 gene were having 3-fold increased risk of pharyngeal cancer. Whereas null genotype of GSTT1 gene was having 2 times increased risk. GSTM/GSTT both null genotype was having more than 5 times increased association with pharyngeal cancer. Presence of all three gene variants showed very 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 pharyngeal cancer susceptibility in Pashtun population.
Esophageal cancer (EC): Individuals with CC and TC genotypes of CYP1A1 rs4646903 polymorphism have strong and significantly higher risk of EC (OR): 15.709, 95%CI: 6.065-40.686, OR: 3.25695%CI: 1.902-5.574 respectively). The 'C allele was strongly associated with the disease (P < 0.0001). Null genotypes of both GSTM1 and GSTT1 genes were having non-significant association with esophageal cancer. Association of two gene combination was also weak and non-significant, except when both genes were absent (both null genotype). Combined presence of all three gene variants showed strong and significant association. Our findings suggest that presence of the 'C allele of rs4646903 (T>C) may be one of the risk alleles for EC susceptibility; whereas GSTM1 and GSTT1 null genotypes also contributes towards increased...