Abstract
Genetic variation within microRNA (miRNA) may result in its abnormal folding or aberrant expression, contributing to colorectal turmorigenesis and metastasis. However, the association of six polymorphisms (miR-608 rs4919510, miR-499a rs3746444, miR-146a rs2910164, pre-miR-143 rs41291957, pre-miR-124-1 rs531564 and pre-miR-26a-1 rs7372209) with colorectal cancer (CRC) risk, therapeutic response and survival remains unclear. A retrospective study was carried out to investigate the association in 1358 0-III stage resected CRC patients and 1079 healthy controls using Sequenom's MassARRAY platform. The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemo-radiotherapy in co-dominant, allele and dominant models; moreover, there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; additionally, a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively. Our findings indicated that rs4919510 allele G and genotype GG were protective factors for 0-II stage CRC, rs7372209 and rs531564 could decrease RFS in II stage individuals and resected CRC patients receiving adjuvant chemo-radiology.
Highlights
Accumulating experimental evidence shows that microRNAs are crucial expression micromanagers of genes associated with colorectal cancer (CRC) [1,2,3]
The results showed that rs4919510 was significantly associated with a decreased susceptibility to CRC in co-dominant, allele and recessive genetic models, and the protective role of rs4919510 allele G and genotype GG was more pronounced among stage 0-II cases; significant association between rs531564 and poor RFS was observed in cases undergoing adjuvant chemoradiotherapy in co-dominant, allele and dominant models; there was a positive association between rs7372209 and recurrence-free survival in stage II cases in co-dominant and over-dominant models; a cumulative effect of rs531564 and rs7372209 at-risk genotypes with hazard ratio at 1.30 and 1.95 for one and two at-risk genotypes was examined in stage II cases, respectively
We found a decreased susceptibility to 0-II stage CRC among patient harbored rs4919510 genotype GG and allele G, worse clinical RFS among patients with mutants of rs531564 and rs7372209 was observed in comparison with the genotype CC of the two loci, especially in patients undergoing adjuvant chemoradiotherapy and II stage patients
Summary
Accumulating experimental evidence shows that microRNAs (miRNAs) are crucial expression micromanagers of genes associated with colorectal cancer (CRC) [1,2,3]. They can post-transcriptionally destabilize the target gene and inhibit translation of the protein by binding to the target mRNAs 3’-untranslated region (UTR) [4]. Several studies reported association of polymorphisms within miRNA and susceptibility, drug response and survival of CRC [8,9,10] These studies were performed in heterogeneous population with www.impactjournals.com/oncotarget small sample size, leading to contradictory conclusions with low statistic power. Lack of the association was observed between rs2910164 and risk of CRC in a total of 621 European subjects [10]
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