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Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development

  • Milica Lj. Stojkovic Lalosevic
  • Vesna M. Coric
  • Tatjana D. Pekmezovic
  • Tatjana P. Simic
  • Marija S. Pljesa Ercegovac
  • Aleksandra R. Pavlovic Markovic
  • Zoran V. KrivokapicEmail author
Original Article
  • 17 Downloads

Abstract

Glutathione-S transferases (GSTs) are xenobiotic-conjugation enzymes involved in the detoxification process of heterocyclic aromatic amines and polycyclic aromatic hydrocarbons, widely recognized risk factors of colorectal cancer (CRC) development. Polymorphism in GSTs often leads to alteration or complete lack of enzyme activity, which might have an effect on CRC carcinogenesis. Aim of this study was to investigate GST gene variants as risk factors in patients with CRC. A total of 523 CRC patients administered for surgical resection and 400 matched controls were included. Deletion polymorphism of GSTs M1 and T1 was investigated by polymerase chain reaction. Single nucleotide polymorphism of GST A1 and P1 was investigated by restriction fragment length polymorphism method. The association between GST genotype and risk of CRC development was found in carriers of GSTT1-null and GSTP1-variant genotypes individually (p = 0.050 and p = 0.016, respectively). Furthermore, statistically significant association was found when combination of GSTP1-variant genotype with any of other three common GST genotypes was analyzed with respect to CRC susceptibility. Additionally, patients with combined GSTM1-null/GSTT1-null/GSTA1 low-activity/GSTP1-variant genotype showed 2.71-fold increased risk of developing CRC (p = 0.037). This study supports hypothesis that GST polymorphisms might have an important role in the process of the CRC development. Additionally, GSTM1-null/ GSTT1-null/ GSTA1 low-activity/ GSTP1-variant genotype could be combination of GST genotypes whose carriers are more prone to CRC development.

Keywords

Colorectal cancer Glutathione-S transferases GST polymorphism Carcinogenesis Colorectal cancer development 

Notes

Acknowledgments

This work has been supported by a Grant No OI175030 from Ministry of Education, Science and Technological Development Republic of Serbia.

Compliance with Ethical Standards

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of Interest

Authors have no conflict of interest to declare.

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Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  • Milica Lj. Stojkovic Lalosevic
    • 1
  • Vesna M. Coric
    • 2
    • 3
  • Tatjana D. Pekmezovic
    • 3
    • 4
  • Tatjana P. Simic
    • 2
    • 3
  • Marija S. Pljesa Ercegovac
    • 2
    • 3
  • Aleksandra R. Pavlovic Markovic
    • 1
    • 3
  • Zoran V. Krivokapic
    • 3
    • 5
    Email author
  1. 1.Clinic of gastroenterology and hepatology, Clinical center of SerbiaBelgradeSerbia
  2. 2.Institute of Medical and Clinical biochemistryBelgradeSerbia
  3. 3.Faculty of MedicineUniversity of BelgradeBelgradeSerbia
  4. 4.Institute of EpidemiologyBelgradeSerbia
  5. 5.Clinic for Digestive surgery, Clinical center of SerbiaBelgradeSerbia

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