Glutathione S Transferase P1, 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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Published in:International Medical Journal Vol. 18; no. 4; pp. 279 - 283
Main Authors: Mohd Shahpudin, Siti Nurfatimah, Mustapha, Mohd Aminudin, Abdul Aziz, Ahmad Aizat, Murali Krishna, Bhavaraju Venkata, Chatar Singh, Gurjeet Kaur, Naik, Venkatesh R., Zakaria, Zaidi, Mohd Sidek, Ahmad Shanwani, Abu Hassan, Mohammad Radz, Ankathi, Ravindran
Format: pictorial research tables/charts Journal Article
Published: Japan International Cultural Exchange Foundation Dec2011
Online Access:View this record in EBSCOhost
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      dt: Dec2011
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      pub: Japan International Cultural Exchange Foundation
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        atl: Glutathione S Transferase P1, MI and TI Genotypes and Risk for Colorectal Cancer Development in Malaysian Population.
      aug:
        au:
          Mohd Shahpudin, Siti Nurfatimah
          Mustapha, Mohd Aminudin
          Abdul Aziz, Ahmad Aizat
          Murali Krishna, Bhavaraju Venkata
          Chatar Singh, Gurjeet Kaur
          Naik, Venkatesh R.
          Zakaria, Zaidi
          Mohd Sidek, Ahmad Shanwani
          Abu Hassan, Mohammad Radz
          Ankathi, Ravindran
        affil: Human Genome Centre, Universiti Sains Malaysia, Health Campus 16150 Kubang Kerian, Kelantan, Malaysia
      sug:
        subj:
          Colorectal Neoplasms Familial and Genetic
          Genotype
          Enzymes
          Glutathione
          Malaysia
          Human
          Funding Source
          Colorectal Neoplasms Physiopathology
          DNA Analysis
          Polymerase Chain Reaction
          Odds Ratio
          Confidence Intervals
          Case Control Studies
          Male
          Female
          Adult
          Middle Age
          Aged
          Descriptive Statistics
          Adult: 19-44 years
          Middle Aged: 45-64 years
          Aged: 65+ years
          Male
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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