• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.3
• /
• pp.1145-1150
• /
• 2015

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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.6
• /
• pp.3925-3929
• /
• 2013

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2699-2705
• /
• 2014

This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers.