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Role of GSTM1 Copy Number Variant in the Prognosis of Thai Colorectal Cancer Patients Treated with 5-FU-based Chemotherapy

  • Pongtheerat, Tanett (Unit of Biochemistry, Department of Medical Sciences, Faculty of Science, Rangsit University) ;
  • Saelee, Pensri (Research Division, National Cancer Institute of Thailand)
  • Published : 2016.10.01

Abstract

Background: Glutathione S-transferase M1 (GSTM1) is involved in the detoxification of carcinogenic agents. DNA copy number variants of GSTM1 may be associated with cancer progression and may result in reduced survival time of various cancers. Determination of DNA copy number variants was here used to assess the association between GSTM1 copy number variant and pathological status and survival time of colorectal-cancer patients treated with 5-fluorouracil-based chemotherapy. Methods: One hundred thirteen Thai colorectal-cancer patients were investigated for GSTM1 copy number variant by real-time PCR. Relationships between gene copy number variants and clinico-pathological parameters were determined. Result: Associations were evident between GSTM1 copy number and stage of tumor (P = 0.026) and metastasis at diagnosis (P = 0.049), with odds ratio values of 0.2 and 0.3 respectively. Conclusions: GSTM1 copy number variant was here not related with reduced overall survival for the colorectal-cancer patients receiving 5-FU-based chemotherapy.

Keywords

Glutathione S-transferase M1;DNA copy number variant;Colorectal cancer;5-FU-based Chemotherapy

References

  1. Aschele C, Lonardi S, Monfardini S (2002). Thymidylate Synthase expression as a predictor of clinical response to fluoropyrimidine-based chemotherapy in advanced colorectal cancer. Cancer Treat Rev, 28, 27-47. https://doi.org/10.1053/ctrv.2002.0253
  2. Cheng X, Kigawa J, Minagawa Y, et al (1997). Glutathione S-transferase-pi expression and glutathione concentration in ovarian carcinoma before and after chemotherapy. Cancer, 79, 521-7. https://doi.org/10.1002/(SICI)1097-0142(19970201)79:3<521::AID-CNCR14>3.0.CO;2-5
  3. Covault J, Abreu C, Kranzler H, Oncken C (2003). Quantitative real-time PCR for gene dosage determinations in microdeletion genotypes. Biotechniques, 35, 594-8.
  4. Depeille P, Cuq P, Mary S, et al (2004) Glutathione S-transferase M1 and multidrug resistance protein 1 act in synergy to protect melanoma cells from vincristine effects. Mol Pharmacol, 65, 897-905. https://doi.org/10.1124/mol.65.4.897
  5. Funke S, Brenner H, Chang-Claude J (2008) Pharmacogenetics in colorectal cancer: A systematic review. Pharmacogenomics, 9, 1079-99. https://doi.org/10.2217/14622416.9.8.1079
  6. He Y, Hoskins JM, McLeod HL (2011). Copy number variants in pharmacogenetic genes. Trends Mol Med, 17, 244-51. https://doi.org/10.1016/j.molmed.2011.01.007
  7. Imsamran W, Chaiwerawattana A,Wiangnon S, et al (2015). Cancer in Thailand Vol VIII. Bangkok: New Thammada Press (Thailand) Co., Ltd.
  8. Lai CY, Hsieh LL, Sung FC, (2013). Tumor site- and stage-specific associations between allelic variants of glutathione S-transferase and DNA-repair genes and overall survival in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. PLoS One, 8, e69039. doi:10.1371/journal.pone. 0069039. https://doi.org/10.1371/journal.pone.0069039
  9. Mccarroll SA, Altshuler DM (2007). Copy-number variation and association studies of human disease. Nature Genet, 39, 37-42. https://doi.org/10.1038/ng2080
  10. Mohelnikova-Duchonova B, Melichar B, Soucek P, (2014). FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World J Gastroenterol, 20, 10316-630. https://doi.org/10.3748/wjg.v20.i30.10316
  11. Norskov MS, Frikke-Schmidt R, Loft S, Tybjaerg-Hansen A, (2009). High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals. Clin Biochem, 42, 201-9. https://doi.org/10.1016/j.clinbiochem.2008.10.020
  12. Pongtheerat T, Chaksangchaichot P, Saelee P, (2013). Prognosis in Thai colorectal-cancer patients with GSTM1 and GSTT1 copy number variation. Eur J Oncol, 18, 189-95.
  13. Rebbeck TR, (1997). Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev, 6, 733-43.
  14. Satta T, Isobe K, Yamauchi M, Nakashima I, Takagi H, (1992). Expression of MDR1 and glutathione S transferase-pi genes and chemosensitivities in human gastrointestinal cancer. Cancer, 69, 941-46. https://doi.org/10.1002/1097-0142(19920215)69:4<941::AID-CNCR2820690418>3.0.CO;2-H
  15. Seo BG, Kwon HC, Oh SY, et al (2009). Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIRI. Oncol Rep, 22, 127-36.
  16. Sinicrope FA, Foster NR, Thibodeau SN, et al (2011). DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst, 103, 863-75. https://doi.org/10.1093/jnci/djr153
  17. Sprenger R, Schlagenhaufer R, Kerb R, et al (2000). Characterization of the glutathione S-transferase GSTT1 deletion: discrimination of all genotypes by polymerase chain reaction indicates a trimodular genotype-phenotype correlation. Pharmacogenetics, 10, 557-65. https://doi.org/10.1097/00008571-200008000-00009
  18. Stoehlmacher J, Park DJ, Zhang W, et al. (2002). Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst, 94, 936-42. https://doi.org/10.1093/jnci/94.12.936