Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan

被引:85
作者
Boni, V. [2 ]
Zarate, R. [1 ]
Villa, J. C. [3 ]
Bandres, E. [1 ]
Gomez, M. A. [3 ]
Maiello, E. [2 ]
Garcia-Foncillas, J. [1 ]
Aranda, E. [3 ]
机构
[1] Univ Navarra, Ctr Appl Med Res, Lab Pharmacogen, Dept Oncol, Pamplona 31008, Spain
[2] Casa Sollievo Sofferenza, Dept Haematol & Oncol, Oncol Unit, San Giovanni Rotondo, Italy
[3] Hosp Univ Reina Sofia, Med Oncol Serv, Cordoba 14004, Spain
关键词
microRNA; single-nucleotide polymorphism; tumor response; colorectal cancer; 5-FU; irinotecan; MICRORNA EXPRESSION; GENES; RNA; PROLIFERATION; REPRESSION; INSIGHT; PATHWAY; GROWTH; RISK;
D O I
10.1038/tpj.2010.58
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. The Pharmacogenomics Journal (2011) 11, 429-436; doi:10.1038/tpj.2010.58; published online 29 June 2010
引用
收藏
页码:429 / 436
页数:8
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