Genetic Polymorphisms in Pre-microRNA Genes as Prognostic Markers of Colorectal Cancer

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 21; no. 1; pp. 217 - 227
• Main Authors: JINLIANG XING, SHAOGUI WAN, HUSHAN YANG, FENG ZHOU, FALIN QU, BINGSHAN LI, MYERS, Ronald E, XIAOYING FU, PALAZZO, Juan P, XIANLI HE, ZHINAN CHEN
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.01.2012
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Colorectal Neoplasms - genetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Humans; Male; Medical sciences; MicroRNAs - genetics; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Young Adult; Rectal disease; RNA interference; Prognosis; Genetic variability; Genetic marker; Colorectal cancer; Micro RNA; Genotype; Malignant tumor; Colonic disease; Gene silencing; Cancerology; Digestive diseases; Intestinal disease; Cancer; Polymorphism
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-11-0624

Cumulative data have shown that microRNAs (miRNA) 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. We analyzed the effects of seven single-nucleotide polymorphisms (SNP) in pre-miRNA genes on the prognosis of a Chinese population with 408 CRC patients with surgically-resected adenocarcinoma. 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 with the homozygous wild-type genotype, the variant-containing genotypes of this SNP were significantly associated with both the overall survival (HR = 2.12, 95% CI = 1.34-3.34, P = 0.001) and the recurrence-free survival (HR = 1.59, 95% CI = 1.08-2.36, 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). 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. This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC.