miR-608 rs4919510多态性可能会根据癌症类型改变癌症易感性。

The miR-608 rs4919510 polymorphism may modify cancer susceptibility based on type.

作者信息

Wu Shuangshuang, Yuan Weiyan, Shen Yu, Lu Xiao, Li Yue, Tian Tian, Jiang Liying, Zhuang Xun, Wu Jianqing, Chu Minjie

机构信息

1 Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

2 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Tumour Biol. 2017 Jun;39(6):1010428317703819. doi: 10.1177/1010428317703819.

DOI:10.1177/1010428317703819

PMID:28653886

Abstract

Previous meta-analysis has not shown different effects of miR-608 rs4919510 polymorphism in specific cancer types and reported no significant association between rs4919510 and cancer risk among Chinese. However, more recent findings have been inconsistent. Therefore, we performed an updated meta-analysis to examine whether this polymorphism is associated with cancer risk based on ethnicity and type. A total of 18 case-control studies, comprising 12,517 cases and 15,624 controls, were included in our study. Surprisingly, in contrast with previous meta-analysis, a significant association between the rs4919510 polymorphism and cancer risk was observed in Chinese (CG vs CC: odds ratio = 1.11; 95% confidence interval = 1.04-1.19). In further stratified analyses based on cancer type, rs4919510 was significantly associated with an increased risk of papillary thyroid cancer (CG vs CC: odds ratio = 1.25; 95% confidence interval = 1.01-1.54) and exhibited borderline significant associations with increased risk of gastric cancer (GG vs CC: odds ratio = 1.27; 95% confidence interval = 1.00-1.62) and lung cancer (CG vs CC: odds ratio = 1.14; 95% confidence interval = 0.99-1.32), but a decreased risk of colorectal cancer (GG vs CC: odds ratio = 0.74; 95% confidence interval = 0.60-0.91). Moreover, the RegulomeDB database indicated that rs4919510 may affect the expression of two nearby genes ( SEMA4G and MRPL43), and the Cancer Genome Atlas database revealed that the expression level of SEMA4G was significantly lower in colorectal cancer and lung cancer tissues than that in adjacent non-tumour tissues, while the expression level of SEMA4G was significantly higher in gastric cancer tissues than that in adjacent non-tumour tissues. These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.

摘要

既往的荟萃分析未显示miR - 608 rs4919510多态性在特定癌症类型中有不同影响，且报道称在中国人群中rs4919510与癌症风险之间无显著关联。然而，最近的研究结果并不一致。因此，我们进行了一项更新的荟萃分析，以研究基于种族和癌症类型，这种多态性是否与癌症风险相关。我们的研究共纳入了18项病例对照研究，包括12517例病例和15624例对照。令人惊讶的是，与既往的荟萃分析相反，在中国人群中观察到rs4919510多态性与癌症风险之间存在显著关联（CG与CC相比：比值比 = 1.11；95%置信区间 = 1.04 - 1.19）。在基于癌症类型的进一步分层分析中，rs4919510与甲状腺乳头状癌风险增加显著相关（CG与CC相比：比值比 = 1.25；95%置信区间 = 1.01 - 1.54），与胃癌风险增加呈临界显著关联（GG与CC相比：比值比 = 1.27；95%置信区间 = 1.00 - 1.62）以及与肺癌风险增加呈临界显著关联（CG与CC相比：比值比 = 1.14；95%置信区间 = 0.99 - 1.32），但与结直肠癌风险降低相关（GG与CC相比：比值比 = 0.74；95%置信区间 = 0.60 - 0.91）。此外，RegulomeDB数据库表明rs4919510可能影响两个邻近基因（SEMA4G和MRPL43）的表达，癌症基因组图谱数据库显示，SEMA4G在结直肠癌和肺癌组织中的表达水平显著低于相邻非肿瘤组织，而SEMA4G在胃癌组织中的表达水平显著高于相邻非肿瘤组织。这些发现提供了证据，表明miR - 608 rs4919510多态性可能以癌症类型特异性的方式改变癌症易感性。此外，SEMA4G可能作为癌基因或肿瘤抑制基因，以癌症类型特异性的方式调节肿瘤发展。有必要进行进一步的实验评估研究。