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

icecream 添加于 2012-12-26 09:25 | 2027 次阅读 | 0 个评论

作者
Xing J, Wan S, Zhou F, Qu F, Li B, Myers RE, Fu X, Palazzo JP, He X, Chen Z, Yang H
摘要
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. IMPACT: This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC.
详细资料
- 关键词: Adult; Aged; Aged, 80 and over; Colorectal Neoplasms/*genetics; Female; Genotype; Humans; Male; MicroRNAs/*genetics; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Young Adult
- 文献种类:期刊
- 期刊名称: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
- 期刊缩写: Cancer Epidemiol Biomarkers Prev
- 期卷页: 2012年第21卷第1期 217-227页
- 地址: State Key Laboratory of Cancer Biology, Cell Engineering Research Center & Department of Cell Biology, Tangdu Hospital, Fourth Military Medical University, Xi\'an, China
- ISBN: 1055-9965
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