Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population

Background: Colorectal cancer (CRC) is a multifactorial disease with factors including dietary and lifestyle habits and genetic predisposition contributing to its etiopathogenesis. Even though the genetic predisposing factors are still unclear, genetic polymorphisms of genes encoding enzymes involve...

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Main Authors: Siti Nurfatimah, Mohd Shahpudin, Mohd Aminudin, Mustapha, Ahmad Aizat, Abdul Aziz, Murali Krishana, Bahavaraju Venkata, Chatar Singh, Gurjeet Kaur, Venkatesh R, Naik, Zaidi, Zakaria, Ahmad Shanwani, Mohd Sidek, Mohammad Radzi, Abu Hassan, Ankathil, Ravindran
Format: Article
Language:English
Published: Japan International Cultural Exchange Foundation & Japan Health Sciences University 2011
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spelling unimas-7002016-04-12T02:33:04Z http://ir.unimas.my/700/ Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population Siti Nurfatimah, Mohd Shahpudin Mohd Aminudin, Mustapha Ahmad Aizat, Abdul Aziz Murali Krishana, Bahavaraju Venkata Chatar Singh, Gurjeet Kaur Venkatesh R, Naik Zaidi, Zakaria Ahmad Shanwani, Mohd Sidek Mohammad Radzi, Abu Hassan Ankathil, Ravindran Q Science (General) R Medicine (General) Background: Colorectal cancer (CRC) is a multifactorial disease with factors including dietary and lifestyle habits and genetic predisposition contributing to its etiopathogenesis. Even though the genetic predisposing factors are still unclear, genetic polymorphisms of genes encoding enzymes involved in xenobiotic metabolic pathways that activate or inactivate dietary carcinogens have been proposed as candidate genes. Three members of the Gluthathione S-Transferase (GSTs) family GSTPI, GSTT1 and GSTM1 have been analyzed in Malaysian population for polymorphic variants, and to elucidate their role in colorectal carcinogenesis. Objective: To determine the frequencies of GSTPI, GSTTI and GSTMI genotypes in 111 histopathologically confirmed CRC patients and 128 healthy controls and to evaluate the association risk of GSTPI, GSTTI and GSTMI genotypes on CRC predisposition. Material and Methods: Peripheral blood from the study subjects were collected in EDTA tubes and genomic DNA extracted using QIAGEN kit. The GSTPI IlelO5Val polymorphism was analyzed by PCR-RFLP technique using BsmAl restriction enzyme. The presence or absence of GSTM1 and GSTT1, genes were determined using a multiplex PCR protocol with albumin as the housekeeping gene. The resulting PCR fragments were separated on 2.0% agarose gel for GSTPI and 3.0% agarose gel electrophoresis for the GSTT1 and GSTM1. Results and Conclusion: On evaluating the CRC risk association with variant genotypes singly, GSTTI null genotype was associated significantly with an elevated risk (OR 1.804, 95%CI: 1.065-3.361, p=0027). When the polymorphic genotypes were analyzed in combination, the combination genotypes of GSTPI Val/Val/GSTM+/GSTTI÷ (OR 4.000), Val/Val/GSTMI-/GSTTI- (OR 3.000), and GSTPI Ile/Ile/GSTMI+/GSTTI- (OR 2.833) showed higher associated risk for CRC susceptibility, however the risk values were not statistically significant. Further studies involving larger sample size may help to identify the more specific risk groups and to determine factors of importance in CRC development. Japan International Cultural Exchange Foundation & Japan Health Sciences University 2011-12 Article NonPeerReviewed text en http://ir.unimas.my/700/1/glutathione%20S%20transferase%20PI.pdf Siti Nurfatimah, Mohd Shahpudin and Mohd Aminudin, Mustapha and Ahmad Aizat, Abdul Aziz and Murali Krishana, Bahavaraju Venkata and Chatar Singh, Gurjeet Kaur and Venkatesh R, Naik and Zaidi, Zakaria and Ahmad Shanwani, Mohd Sidek and Mohammad Radzi, Abu Hassan and Ankathil, Ravindran (2011) Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population. International Medical Journal. , 18 (4). pp. 279-282. http://connection.ebscohost.com/c/articles/71093480/glutathione-s-transferase-p1-mi-ti-genotypes-risk-colorectal-cancer-development-malaysian-population
repository_type Digital Repository
institution_category Local University
institution Universiti Malaysia Sarawak
building UNIMAS Institutional Repository
collection Online Access
language English
topic Q Science (General)
R Medicine (General)
spellingShingle Q Science (General)
R Medicine (General)
Siti Nurfatimah, Mohd Shahpudin
Mohd Aminudin, Mustapha
Ahmad Aizat, Abdul Aziz
Murali Krishana, Bahavaraju Venkata
Chatar Singh, Gurjeet Kaur
Venkatesh R, Naik
Zaidi, Zakaria
Ahmad Shanwani, Mohd Sidek
Mohammad Radzi, Abu Hassan
Ankathil, Ravindran
Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
description Background: Colorectal cancer (CRC) is a multifactorial disease with factors including dietary and lifestyle habits and genetic predisposition contributing to its etiopathogenesis. Even though the genetic predisposing factors are still unclear, genetic polymorphisms of genes encoding enzymes involved in xenobiotic metabolic pathways that activate or inactivate dietary carcinogens have been proposed as candidate genes. Three members of the Gluthathione S-Transferase (GSTs) family GSTPI, GSTT1 and GSTM1 have been analyzed in Malaysian population for polymorphic variants, and to elucidate their role in colorectal carcinogenesis. Objective: To determine the frequencies of GSTPI, GSTTI and GSTMI genotypes in 111 histopathologically confirmed CRC patients and 128 healthy controls and to evaluate the association risk of GSTPI, GSTTI and GSTMI genotypes on CRC predisposition. Material and Methods: Peripheral blood from the study subjects were collected in EDTA tubes and genomic DNA extracted using QIAGEN kit. The GSTPI IlelO5Val polymorphism was analyzed by PCR-RFLP technique using BsmAl restriction enzyme. The presence or absence of GSTM1 and GSTT1, genes were determined using a multiplex PCR protocol with albumin as the housekeeping gene. The resulting PCR fragments were separated on 2.0% agarose gel for GSTPI and 3.0% agarose gel electrophoresis for the GSTT1 and GSTM1. Results and Conclusion: On evaluating the CRC risk association with variant genotypes singly, GSTTI null genotype was associated significantly with an elevated risk (OR 1.804, 95%CI: 1.065-3.361, p=0027). When the polymorphic genotypes were analyzed in combination, the combination genotypes of GSTPI Val/Val/GSTM+/GSTTI÷ (OR 4.000), Val/Val/GSTMI-/GSTTI- (OR 3.000), and GSTPI Ile/Ile/GSTMI+/GSTTI- (OR 2.833) showed higher associated risk for CRC susceptibility, however the risk values were not statistically significant. Further studies involving larger sample size may help to identify the more specific risk groups and to determine factors of importance in CRC development.
format Article
author Siti Nurfatimah, Mohd Shahpudin
Mohd Aminudin, Mustapha
Ahmad Aizat, Abdul Aziz
Murali Krishana, Bahavaraju Venkata
Chatar Singh, Gurjeet Kaur
Venkatesh R, Naik
Zaidi, Zakaria
Ahmad Shanwani, Mohd Sidek
Mohammad Radzi, Abu Hassan
Ankathil, Ravindran
author_facet Siti Nurfatimah, Mohd Shahpudin
Mohd Aminudin, Mustapha
Ahmad Aizat, Abdul Aziz
Murali Krishana, Bahavaraju Venkata
Chatar Singh, Gurjeet Kaur
Venkatesh R, Naik
Zaidi, Zakaria
Ahmad Shanwani, Mohd Sidek
Mohammad Radzi, Abu Hassan
Ankathil, Ravindran
author_sort Siti Nurfatimah, Mohd Shahpudin
title Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
title_short Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
title_full Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
title_fullStr Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
title_full_unstemmed Glutathione S tranferase PI, MI and TI genotypes and risk for colorectal cancer development in Malaysian population
title_sort glutathione s tranferase pi, mi and ti genotypes and risk for colorectal cancer development in malaysian population
publisher Japan International Cultural Exchange Foundation & Japan Health Sciences University
publishDate 2011
url http://ir.unimas.my/700/
http://ir.unimas.my/700/
http://ir.unimas.my/700/1/glutathione%20S%20transferase%20PI.pdf
first_indexed 2018-09-06T14:38:17Z
last_indexed 2018-09-06T14:38:17Z
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