Genetic polymorphisms in microRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients

Moubin Lin, Jian Gu, Cathy Eng, Lee M. Ellis, Michelle A. Hildebrandt, Jie Lin, Maosheng Huang, George A. Calin, Dingzhi Wang, Raymond N. DuBois, Ernest T. Hawk, Xifeng Wu

    Research output: Contribution to journalArticle

    56 Scopus citations

    Abstract

    Purpose: To evaluate the effects of single-nucleotide polymorphisms (SNP) in microRNA-related genes on clinical outcomes in patients with colorectal cancer (CRC) receiving first-line fluoropyrimidine-based chemotherapy. Experimental Design: Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097 patients with CRC recruited at the University of Texas MD Anderson Cancer Center (Houston, TX). Patients were enrolled between 1990 and 2008 and last follow-up was in 2010. The associations between genotypes and recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) stratified by clinical stage were analyzed in 741 newly diagnosed patients (diagnosed within 1 year) and replicated the findings in an additional 356 patients. Results: In patients with stage III disease, mir608:rs4919510 was associated with increased risk for both recurrence [HR, 2.72; 95% confidence interval (CI), 1.38-5.33] and death (HR, 3.53; 95%CI, 1.42-8.73). The associations were confirmed in the replication set, and the combined HRs for training and replication sets were 1.65 (95% CI, 1.13-2.41) for recurrence and 1.96 (95% CI, 1.19-3.21) for death, respectively. The mir219-1:rs213210 showed consistent association with death in the training set (HR, 3.86; 95% CI, 1.33-11.22), the replication set (HR, 3.33; 95% CI, 1.39-7.98), and combined data set (HR, 3.22; 95% CI, 1.70-6.10). In combined analysis of these two SNPs, patients carrying the variant genotypes at both sites exhibited a 5.6-fold increased risk of death. Conclusion: Genetic polymorphisms in the microRNA pathway may predict prognosis in patients with stage III CRC treated with fluoropyrimidine-based chemotherapy.

    Original languageEnglish (US)
    Pages (from-to)3982-3991
    Number of pages10
    JournalClinical Cancer Research
    Volume18
    Issue number14
    DOIs
    StatePublished - Jul 15 2012

      Fingerprint

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Lin, M., Gu, J., Eng, C., Ellis, L. M., Hildebrandt, M. A., Lin, J., Huang, M., Calin, G. A., Wang, D., DuBois, R. N., Hawk, E. T., & Wu, X. (2012). Genetic polymorphisms in microRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients. Clinical Cancer Research, 18(14), 3982-3991. https://doi.org/10.1158/1078-0432.CCR-11-2951