Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer
Cette étude chinoise (408 cas) montre une association entre des polymorphismes à simple nucléotide de gènes codant pour des pré-micro-ARNs et la survie des patients ayant subi la résection d'un adénocarcinome colorectal
Background: Cumulative data has shown that microRNAs (miRNAs) are involved in the etiology and prognosis of colorectal cancer (CRC). Genetic polymorphisms in pre-miRNA genes may influence the biogenesis and functions of their host miRNAs. However, whether these polymorphisms are associated with CRC prognosis remains unknown. Methods: We analyzed the effects of seven single nucleotide polymorphisms (SNPs) in pre-miRNA genes on the prognosis of a Chinese population with 408 CRC patients with surgically-resected adenocarcinoma. Results: Two SNPs were identified to be significantly associated with recurrence-free survival and overall survival of the patients. The most significant SNP was rs6505162 in pre-miR-423. Compared to the homozygous wild-type genotype, the variant-containing genotypes of this SNP were significantly associated with both the overall survival (HR=2.12, 95% CI1.34--3.34, P=0.001) and the recurrence-free survival (HR=1.59, 95% CI1.08--2.36, P=0.019). Another SNP, rs4919510 in pre-miR-608, was also associated with altered recurrence-free survival (HR=0.61, 95% CI 0.41-0.92, P=0.017). These effects were evident only in patients receiving chemotherapy but not in those without chemotherapy. In addition, the combined analysis of the two SNPs conferred a 2.84-fold (95% CI 1.50-5.37, P=0.001) increased risk of recurrence and/or death. Similarly, this effect was only prominent in those receiving chemotherapy (P<0.001) but not in those without chemotherapy (P=0.999). Conclusions: Our data suggest that genetic polymorphisms in pre-miRNA genes may impact CRC prognosis especially in patients receiving chemotherapy, a finding that warrants further independent validation. Impact: This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC.
Cancer Epidemiology Biomarkers & Prevention , résumé, 2011