Genetic variations in microRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients
Menée sur 1 097 patients atteints d'un adénocarcinome colorectal de stade III et recevant une chimiothérapie de première ligne à base de fluoropyrimidine, cette étude évalue l'association entre 41 polymorphismes à simple nucléotide de 26 gènes codant pour des microARNs et la survie des patients
Purpose: To evaluate the effects of single-nucleotide polymorphisms (SNPs) in microRNA-related genes on clinical outcomes in colorectal cancer (CRC) patients receiving first-line fluoropyrimidine-based chemotherapy. Experimental Design: Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097 CRC patients recruited at the University of Texas MD Anderson Cancer Center. 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 additional 356 patients. Results: In patients with stage III disease, mir608:rs4919510 was associated with increased risk for both recurrence (HR=2.72; 95%CI, 1.38 to 5.33) and death (HR=3.53; 95%CI, 1.42 to 8.73). The associations were confirmed in the replication set and the combined HR for training and replication sets was 1.65 (95% CI, 1.13 to 2.41) for recurrence and 1.96 (95%CI, 1.19 to 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 to11.22), the replication set (HR = 3.33; 95% CI, 1.39 to 7.98) and combined dataset (HR = 3.22; 95% CI, 1.70 to 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 stage III CRC patients treated with fluoropyrimidine-based chemotherapy.
Clinical Cancer Research , résumé, 2012