Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer.
BACKGROUND
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.


METHODS
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.


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 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).


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.


CONCLUSIONS
This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC.
State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Jinliang
J
Xing
Shaogui
S
Wan
Feng
F
Zhou
Falin
F
Qu
Bingshan
B
Li
Ronald E
RE
Myers
Xiaoying
X
Fu
Juan P
JP
Palazzo
Xianli
X
He
Zhinan
Z
Chen
Hushan
H
Yang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D055815:Young Adult
D035683:MicroRNAs