Yi De-Hui, Wang Ben-Gang, Zhong Xin-Ping, Liu Hao, Liu Yong-Feng
Hepatobiliary Surgery and Department 1 of General Surgery, The First Affiliated Hospital of China Medical University, North Nanjing Street #155, Shenyang, 110001, Liaoning Province, China.
Tumour Biol. 2014 Dec;35(12):11967-75. doi: 10.1007/s13277-014-2493-9. Epub 2014 Sep 9.
The promoter region of the microRNA pri-miR-34b/c has a potentially functional polymorphism, rs4938723, located in a typical CpG island. Studies of the association between pri-miR-34b/c rs4938723 polymorphism and risks of various cancers have had inconsistent results. We therefore conducted a meta-analysis of nine studies that included 6,036 cancer patients and 7,490 controls to address this association. Overall, this meta-analysis showed the pri-miR-34b/c rs4938723 TC heterozygote to be significantly associated with increased risk of overall cancers compared with the wild-type TT genotype (P = 0.010, odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.18). In stratified analysis, the TC heterozygote was significantly associated with increased cancers risks in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. The CC genotypes of rs4938723 were also associated with increased hepatocellular cancer risk but associated with decreased colorectal cancer risk in the stratification analysis by a single cancer type. Thus our meta-analysis suggests that the pri-miR-34b/c rs4938723 TC heterozygote contributes to increased overall cancer risks, as well as shown in digestive tract cancers, in hepatocellular cancer, in Asian population and in the large-sample subgroup. This rs4938723 SNP showed an opposite tendency orientation between the hepatocellular cancer and colorectal cancer risks. Large-sample studies are needed to verify our findings.
微小RNA前体pri-miR-34b/c的启动子区域存在一个潜在功能性多态性位点rs4938723，位于一个典型的CpG岛中。关于pri-miR-34b/c rs4938723多态性与各种癌症风险之间关联的研究结果并不一致。因此，我们对9项研究进行了荟萃分析，这些研究共纳入6036例癌症患者和7490例对照，以探讨这种关联。总体而言，该荟萃分析表明，与野生型TT基因型相比，pri-miR-34b/c rs4938723的TC杂合子与总体癌症风险增加显著相关（P = 0.010，优势比（OR）= 1.10，95%置信区间（CI）1.02 - 1.18）。在分层分析中，TC杂合子与消化道癌症、肝细胞癌、亚洲人群以及大样本亚组中的癌症风险增加显著相关。在按单一癌症类型进行的分层分析中，rs4938723的CC基因型也与肝细胞癌风险增加相关，但与结直肠癌风险降低相关。因此，我们的荟萃分析表明，pri-miR-34b/c rs4938723的TC杂合子会导致总体癌症风险增加，在消化道癌症、肝细胞癌、亚洲人群以及大样本亚组中也是如此。这个rs4938723单核苷酸多态性在肝细胞癌和结直肠癌风险之间显示出相反的趋势方向。需要进行大样本研究来验证我们的发现。
