MicroRNAs are non-coding RNAs that can block mRNA translation and influence mRNA 
stability. Recent evidence indicates that miRNA variations can affect drug 
resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics 
research. We investigated associations between polymorphisms in both 
miRNA-containing genomic regions (primary and precursor miRNA) and in genes 
related to miRNA biogenesis with clinical outcome in metastatic colorectal 
cancer (mCRC) patients treated with 5-fluorouracil and irinotecan (CPT-11). 
Eighteen single-nucleotide polymorphisms (SNPs) were analyzed in 61 patients. A 
significant association with tumor response and time to progression (TTP) was 
found for SNP rs7372209 in pri-miR26a-1 (P=0.041 and P=0.017, respectively). The 
genotypes CC and CT were favorable when compared with the TT variant genotype. 
In addition, SNP rs1834306, located in the pri-miR-100 gene, significantly 
correlated with a longer TTP (P=0.04). In the miRNA-biogenesis pathway, a trend 
was identified between SNP rs11077 in the exportin-5 gene and disease control 
rate (P=0.076). This study is the first to suggest a relationship between 
treatment outcome and SNPs in the miRNA-biogenesis machinery, in both primary 
and precursor miRNAs. Our results suggest that miRNA polymorphic variants might 
be useful predictors of clinical outcome in mCRC patients treated with 
5-fluorouracil and CPT-11 combination.