Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer.
Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer.
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pre-microRNA 基因的遗传多态性作为结直肠癌的预后标志物。
DOI：
10.1158/1055-9965.epi-11-0624
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发表时间：
2012-01
期刊：
影响因子：
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通讯作者：
Yang H
中科院分区：
文献类型：
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作者：
Xing J;Wan S;Zhou F;Qu F;Li B;Myers RE;Fu X;Palazzo JP;He X;Chen Z;Yang H
已有研究表明，microRNAs(MiRNAs)参与了结直肠癌(CRC)的病因和预后。前miRNA基因的遗传多态性可能影响其宿主miRNAs的生物发生和功能。然而，这些基因多态是否与结直肠癌的预后相关尚不清楚。我们分析了前miRNA基因的7个单核苷酸多态(SNPs)对408例手术切除的腺癌患者预后的影响。两个单核苷酸多态与患者的无复发生存期和总生存期显著相关。最显著的SNP是miR-423前基因中的rs6505162。与野生型纯合子相比，该变异基因型与总生存率(HR=2.1295%CI1.34~3.34，P=0.001)和无复发生存率(HR=1.59，95%CI1.08~2.36，P=0.019)均显著相关。另一位点突变rs4919510与无复发生存率改变有关(HR=0.61，95%CI0.41~0.92，P=0.017)。这些效果仅在接受化疗的患者中明显，而在未接受化疗的患者中则不明显。此外，两个SNP的联合分析使复发和/或死亡的风险增加了2.84倍(95%可信区间为1.50-5.37，P=0.001)。同样，这种效应只在接受化疗(P<；0.001)的患者中显著，而在未接受化疗的患者(P=0.999)中则不明显。我们的数据表明，miRNA前基因的遗传多态可能会影响CRC的预后，特别是在接受化疗的患者中，这一发现值得进一步独立验证。这是首批显示前miRNA基因SNPs在结直肠癌中的预后作用的研究之一。
Cumulative data has shown that microRNAs (miRNAs) 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. We analyzed the effects of seven single nucleotide polymorphisms (SNPs) in pre-miRNA genes on the prognosis of a Chinese population with 408 CRC patients with surgically-resected adenocarcinoma. 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 to the homozygous wild-type genotype, the variant-containing genotypes of this SNP were significantly associated with both the overall survival (HR=2.12, 95% CI1.34–3.34, P=0.001) and the recurrence-free survival (HR=1.59, 95% CI1.08–2.36, 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). 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. This is one of the first studies showing a prognostic role of pre-miRNA gene SNPs in CRC.