Deletion and Single Nucleotide Polymorphisms in Common Glutathione-S Transferases Contribute to Colorectal Cancer Development
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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.
KeywordsColorectal cancer Glutathione-S transferases GST polymorphism Carcinogenesis Colorectal cancer development
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
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.
- 3.Fleming M, Ravula S, Tatishchev SF, Wang HL (2012) Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol 3(3):153–173Google Scholar
- 6.Ramsey SD, Holmes RS, McDermott CL, Blough DK, Petrin KL, Poole EM et al (2012) A comparison of approaches for association studies of polymorphisms and colorectal Cancer risk. Color Dis Off J Assoc Coloproctol G B Irel 14(9):e573–e586Google Scholar
- 7.Song Q-B, Wang Q, Hu W-G (2014) A systemic review of glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk. Chin J Cancer Res Chung-Kuo Yen Cheng Yen Chiu 26(3):255–267Google Scholar
- 13.Zhunussova G, Zhunusbekova B, Djansugurova L (2015) Association between glutathione S-transferase M1 and T1 polymorphisms and colorectal cancer risk in patients from Kazakhstan. Clin Lab 61(1–2):161–168Google Scholar
- 17.Martínez C, Martín F, Fernández JM, García-Martín E, Sastre J, Díaz-Rubio M, Agúndez JAG, Ladero JM (2006) Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans. Pharmacogenomics 7(5):711–718CrossRefGoogle Scholar
- 20.Tijhuis MJ, Wark PA, Aarts JMMJG, Visker MHPW, Nagengast FM, Kok FJ et al (2005) GSTP1 and GSTA1 polymorphisms interact with cruciferous vegetable intake in colorectal adenoma risk. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 14(12):2943–2951CrossRefGoogle Scholar
- 22.Li J, Xu W, Liu F, Huang S, He M (2015) GSTM1 polymorphism contribute to colorectal cancer in Asian populations: a prospective meta-analysis. Sci Rep 5:12514 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649893/ CrossRefGoogle Scholar
- 28.Strange RC, Fryer AA (1999) The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ 148:231–249Google Scholar
- 29.Deng Q, He B, Pan Y, Sun H, Liu X, Chen J et al (2015) Polymorphisms of GSTA1 contribute to elevated cancer risk: evidence from 15 studies. J BUON off J balk union. Oncologia 20(1):287–295Google Scholar
- 33.Wang J, Jiang J, Zhao Y, Gajalakshmi V, Kuriki K, Suzuki S, Nagaya T, Nakamura S, Akasaka S, Ishikawa H, Tokudome S (2011) Genetic polymorphisms of glutathione S-transferase genes and susceptibility to colorectal cancer: a case-control study in an Indian population. Cancer Epidemiol 35(1):66–72CrossRefGoogle Scholar
- 35.Ateş NA, Tamer L, Ateş C, Ercan B, Elipek T, Ocal K et al (2005) Glutathione S-transferase M1, T1, P1 genotypes and risk for development of colorectal cancer. Biochem Genet 43(3–4):149–163Google Scholar