Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25368035
DOI
10.1093/carcin/bgu224
PII: bgu224
Knihovny.cz E-resources
- MeSH
- Adenocarcinoma drug therapy genetics mortality MeSH
- Fluorouracil therapeutic use MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Colorectal Neoplasms drug therapy genetics mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy genetics mortality MeSH
- MicroRNAs genetics MeSH
- Survival Rate MeSH
- Biomarkers, Tumor genetics MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Antimetabolites, Antineoplastic therapeutic use MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Fluorouracil MeSH
- MicroRNAs MeSH
- MIRN219 microRNA, human MeSH Browser
- MIRN608 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
- Antimetabolites, Antineoplastic MeSH
Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy which improves outcomes in patients. We investigated the effect of single nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have been previously reported as important in prognosis in patients with stage III CRC and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech Republic to evaluate their effect on clinical outcomes. Carriers of the variant T allele in rs213210 and receiving 5-FU chemotherapy were associated with a significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94; 95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor grading, stage III patients carrying the G allele of rs4919510 and undergoing adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20-0.94; adjusted P = 0.03). The present study confirms that variations in miRNA-encoding genes may be an important factor for modulating CRC prognosis and predicting therapy response.
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