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

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Pathology & Oncology Research

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Clinic of gastroenterology and hepatology, Clinical center of Serbia, Belgrade, 11000, Serbia

    Milica Lj. Stojkovic Lalosevic & Aleksandra R. Pavlovic Markovic

  2. Institute of Medical and Clinical biochemistry, Belgrade, 11000, Serbia

    Vesna M. Coric, Tatjana P. Simic & Marija S. Pljesa Ercegovac

  3. Faculty of Medicine, University of Belgrade, Belgrade, 11000, Serbia

    Vesna M. Coric, Tatjana D. Pekmezovic, Tatjana P. Simic, Marija S. Pljesa Ercegovac, Aleksandra R. Pavlovic Markovic & Zoran V. Krivokapic

  4. Institute of Epidemiology, Belgrade, 11000, Serbia

    Tatjana D. Pekmezovic

  5. Clinic for Digestive surgery, Clinical center of Serbia, Belgrade, 11000, Serbia

    Zoran V. Krivokapic

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  1. Milica Lj. Stojkovic Lalosevic
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Correspondence to Zoran V. Krivokapic.

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Stojkovic Lalosevic, M.L., Coric, V.M., Pekmezovic, T.D. et al. Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development. Pathol. Oncol. Res. 25, 1579–1587 (2019). https://doi.org/10.1007/s12253-019-00589-1

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  • DOI: https://doi.org/10.1007/s12253-019-00589-1

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