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Pandith, Arshad A,Hussain, Aashaq,Khan, Mosin S,Shah, Zafar A,Wani, M Saleem,Siddiqi, Mushtaq A Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6
Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.
The XRCC1 Arg399Gln Gene Polymorphism and Risk of Colorectal Cancer: a Study in Kashmir
Khan, Nighat Parveen,Pandith, Arshad Ahmad,Yousuf, Adfar,Khan, Nuzhat Shaheen,Khan, Mosin Saleem,Bhat, Imtiyaz Ahmad,Nazir, Zahoor Wani,Wani, Khursheed Alam,Hussain, Mahboob Ul,Mudassar, Syed Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11
Background: The DNA repair gene XRCC1 Arg399Gln gene polymorphism has been found to be implicated in the development of various cancers, including colorectal cancer (CRC), in different populations. We aimed to determine any association of this polymorphism with the risk of CRC in Kashmir. Materials and Methods: A total of 120 confirmed cases of CRC and 146 healthy cancer free controls from the Kashmiri population were included in this study. Genotyping was carried out by the polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method. Results: Genotype frequencies of XRCC1 Arg399Gln observed in controls were 34.2%, 42.5% and 23.3% for GG (Arg/Arg), GA (Arg/Gln), AA( Gln/Gln), respectively, and 28.3%, 66.7% and 5% in cases, with an odds ratio (OR)=5.7 and 95% confidence interval (CI) =2.3-14.1 (p=0.0001). No significant association of Arg399Gln SNP with any clinicopathological parameters of CRC was found. Conclusions: We found the protective role of 399Gln allele against risk to the development of CRC. The XRCC1 heterozygote status appears to be a strong risk factor for CRC development in the Kashmiri population.
GSTP1 Gene Ile105Val Polymorphism Causes an Elevated Risk for Bladder Carcinogenesis in Smokers
Pandith, Arshad Ahmad,Lateef, Adil,Shahnawaz, Sheikh,Hussain, Aashaq,Malla, Tahir Mohiuddin,Azad, Niyaz,Shehjar, Fahim,Salim, Mosin,Shah, Zafar Amin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11
Background: The glutathione S transferase (GST) family of enzymes plays a vital role in the phase II biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic and polymorphisms in GST genes have been associated with cancer susceptibility and prognosis. GSTP1 is associated with risk of various cancers including bladder cancer. A case control study was conducted to determine the genotype distribution of GSTP1 A>G SNP, to elucidate the possible role of this SNP as a risk factor in urinary bladder cancer (UBC) development and to examine its correlation with clinico-pathologic variables inUBC cases. Materials and Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, we tested the genotype distribution of 180 bladder cancer patients in comparison with 210 cancer-free controls from the same geographical region with matched frequency in age and gender. Results: We did not observe significant genotype differences between the control and bladder cancer patients overall with an odds ratio (OR)=1.23 (p>0.05). The rare allele (AG+GG) was found to be present more in cases (28.3%) than in controls (24%), though the association was not significant (p<0.05). However, a significant risk of more than 2-fold was found for the variant allele (AG+GG) with smokers in cases as compared to controls (p>0.05). Conclusions: Thus, it is evident from our study that GSTP1 SNP is not implicated overall in bladder cancer, but that the rare, valine-related allele is connected with higher susceptibility to bladder cancer in smokers and also males.