1 Department of Urology, Affiliated Zhongda Hospital, Medical School, 2 Surgical Research Center, Medical School, 3 Institute of Urology, Southeast University, Nanjing 210009, China.
Chin J Cancer Res. 2014 Jun;26(3):315-22. doi: 10.3978/j.issn.1000-9604.2014.06.18.
Emerging evidence shows that microRNAs (miRNAs) function as tumor suppressors or oncogenes in human carcinogenesis. A single nucleotide polymorphism (SNP) located in the pri-miRNA promoter may affect the processing and expression of mature miRNA. However, previous studies showed conflicting results regarding the association of hsa-miR-34b/c rs4938723 T > C promoter polymorphism with cancer. Therefore, we conducted a meta-analysis to determine the association of polymorphism with cancer risk.
A computerized search of PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) for publications on hsa-miR-34b/c rs4938723 T > C promoter polymorphism and cancer risk was performed and the genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Test of heterogeneity, cumulative meta-analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis by STATA software 12.0.
There was no significant association between hsa-miR-34b/c rs4938723 polymorphism and overall cancer risk in the comparison models. Moreover, subgroup analysis revealed that the variant CT (OR =1.19, 95% CI: 1.03-1.37) and CC/CT (OR =1.18, 95% CI: 1.03-2.35) genotypes were associated with an increased risk of hepatocellular carcinoma (HCC) compared with wild-type TT genotype. However, a decreased risk of colorectal cancer (CRC) was found in the genetic model of CC/TT (OR =0.66, 95% CI: 0.47-0.92) and CC/CTTT (OR =0.67, 95% CI: 0.49-0.93).
The results suggest that hsa-miR-34b/c rs4938723 polymorphism may play an opposite role in different types of cancer based on current studies, which is the main origin of heterogeneity in this meta-analysis. Further large-scale studies and functional studies between this polymorphism and cancer risk are warranted.
越来越多的证据表明，微小 RNA（miRNA）在人类肿瘤发生中充当肿瘤抑制因子或癌基因。位于 pri-miRNA 启动子中的单核苷酸多态性（SNP）可能影响成熟 miRNA 的加工和表达。然而，先前的研究表明 hsa-miR-34b/c rs4938723 T>C 启动子多态性与癌症之间的关联存在矛盾。因此，我们进行了一项荟萃分析以确定该多态性与癌症风险的关联。
计算机检索 PubMed、Web of Science 和中国知网（CNKI），以获取有关 hsa-miR-34b/c rs4938723 T>C 启动子多态性与癌症风险的出版物，并对基因型数据进行荟萃分析。采用 STATA 软件 12.0 评估比值比（OR）及其 95%置信区间（CI）以评估相关性。异质性检验、累积荟萃分析、敏感性分析和偏倚评估均在荟萃分析中进行。
在比较模型中，hsa-miR-34b/c rs4938723 多态性与总体癌症风险之间无显著相关性。此外，亚组分析显示，与野生型 TT 基因型相比，变体 CT（OR=1.19，95%CI：1.03-1.37）和 CC/CT（OR=1.18，95%CI：1.03-2.35）基因型与肝癌（HCC）风险增加相关。然而，在遗传模型 CC/TT（OR=0.66，95%CI：0.47-0.92）和 CC/CTTT（OR=0.67，95%CI：0.49-0.93）中发现结直肠癌（CRC）的风险降低。
基于目前的研究结果，hsa-miR-34b/c rs4938723 多态性可能在不同类型的癌症中发挥相反的作用，这是该荟萃分析异质性的主要来源。需要进一步进行大规模的研究和该多态性与癌症风险之间的功能研究。
