S Nissar1, A S Sameer2, R Rasool3, N A Chowdri4, F Rashid5. 1. Department of Biochemistry, University of Kashmir; Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences; Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India. 2. Department of Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, KSA. 3. Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. 4. Department of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. 5. Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India.
Abstract
AIM: Glutathione S.transferases. (GSTs) are known to play a pivotal role in the detoxification of potential carcinogens, and their gene variation may alter susceptibility to colorectal cancer. (CRC). The aim of the study was to evaluate the genetic association of GSTM1 and GSTT1 gene deletion/null polymorphism with disease susceptibility and risk development in CRC patients of ethnic Kashmiri population. MATERIALS AND METHODS: Genotype frequencies of GSTM1 and GSTT1 gene deletion/null polymorphism were compared between 160 CRC patients and 200 healthy controls using polymerase chain reaction multiplex. RESULTS: The frequency of GSTM1-null was found to be 76.2% in cases and 81.5% in controls and odds ratio. (OR) = 1.37 (95% confidence interval. [CI]: 0.82-2.28). Likewise, the GSTT1-null genotype was found in 75.5% of cases and 77.5% of controls and the OR = 1.14 (95% CI: 0.76-1.8). The overall association between the GSTM1-null and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). However, individuals with double-null genotype (GSTM1-/GSTT1-) were found to have 3.5-fold increased risk for the development of CRC. Further, the risk genotype (null) of GSTT1 was found to be associated with tumor grade (P = 0.001) and GSTM1 (null) genotype was significantly associated with smoking status (P = 0.004), when compared to the (present) genotype in CRC cases. CONCLUSION: Our results suggest that GSTM1 and GSTT1 gene deletion/null gene polymorphisms are not a key modulators of the risk of developing CRC in Kashmiri population.
AIM: Glutathione S.transferases. (GSTs) are known to play a pivotal role in the detoxification of potential carcinogens, and their gene variation may alter susceptibility to colorectal cancer. (CRC). The aim of the study was to evaluate the genetic association of GSTM1 and GSTT1 gene deletion/null polymorphism with disease susceptibility and risk development in CRC patients of ethnic Kashmiri population. MATERIALS AND METHODS: Genotype frequencies of GSTM1 and GSTT1 gene deletion/null polymorphism were compared between 160 CRC patients and 200 healthy controls using polymerase chain reaction multiplex. RESULTS: The frequency of GSTM1-null was found to be 76.2% in cases and 81.5% in controls and odds ratio. (OR) = 1.37 (95% confidence interval. [CI]: 0.82-2.28). Likewise, the GSTT1-null genotype was found in 75.5% of cases and 77.5% of controls and the OR = 1.14 (95% CI: 0.76-1.8). The overall association between the GSTM1-null and GSTT1-null polymorphism and the CRC cases was found to be insignificant (P < 0.05). However, individuals with double-null genotype (GSTM1-/GSTT1-) were found to have 3.5-fold increased risk for the development of CRC. Further, the risk genotype (null) of GSTT1 was found to be associated with tumor grade (P = 0.001) and GSTM1 (null) genotype was significantly associated with smoking status (P = 0.004), when compared to the (present) genotype in CRC cases. CONCLUSION: Our results suggest that GSTM1 and GSTT1 gene deletion/null gene polymorphisms are not a key modulators of the risk of developing CRC in Kashmiri population.