Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer
- 119 Downloads
Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I 2 = 0 %) and DFS (I 2 = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07–1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03–1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.
KeywordsColorectal cancer Glutathione S-transferase M1 Prognosis
This work was supported by the National Natural Science Foundation (81430062). This work was also supported in part by the program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU and the Priority Academic Program of Jiangsu Higher Education Institutions.
Compliance with ethical standards
Conflicts of interest
- 6.Blumenstein I, Tacke W, Bock H, Filmann N, Lieber E, Zeuzem S, et al. Prevalence of colorectal cancer and its precursor lesions in symptomatic and asymptomatic patients undergoing total colonoscopy: results of a large prospective, multicenter, controlled endoscopy study. Eur J Gastroenterol Hepatol. 2013;25:556–61.CrossRefPubMedGoogle Scholar
- 17.Kap EJ, Richter S, Rudolph A, Jansen L, Ulrich A, Hoffmeister M, et al. Genetic variants in the glutathione S-transferase genes and survival in colorectal cancer patients after chemotherapy and differences according to treatment with oxaliplatin. Pharmacogenet Genomics. 2014;24:340–7.CrossRefPubMedGoogle Scholar
- 18.Negandhi AA, Hyde A, Dicks E, Pollett W, Younghusband BH, Parfrey P, et al. MTHFR Glu429Ala and ERCC5 His46His polymorphisms are associated with prognosis in colorectal cancer patients: analysis of two independent cohorts from Newfoundland. PLoS One. 2013;8:e61469.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, et al. Pharmacogenetic predictors of adverse events and response to chemotherapy in metastatic colorectal cancer: results from North American Gastrointestinal Intergroup Trial N9741. J Clin Oncol. 2010;28:3227–33.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Funke S, Risch A, Nieters A, Hoffmeister M, Stegmaier C, Seiler CM, et al. Genetic polymorphisms in genes related to oxidative stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and survival of rectal cancer patients after radiotherapy. J Cancer Epidemiol. 2009;2009:302047.CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Lai CY, Hsieh LL, Sung FC, Tang R, Bai CH, Wu FY, et al. 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. 2013;8:e69039.CrossRefPubMedPubMedCentralGoogle Scholar