Associations of THBS2 and THBS4 polymorphisms to gastric cancer in a Southeast Chinese population
Associations of THBS2 and THBS4 polymorphisms to gastric cancer in a Southeast Chinese population
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DOI：
10.1016/j.cancergen.2016.04.003
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发表时间：
2016-05-01
期刊：
影响因子：
1.9
通讯作者：
Luo, Xingguang
中科院分区：
文献类型：
--
作者：
Lin, Xiandong;Hu, Don;Luo, Xingguang
Thrombospondin-2 （THBS2）和Thrombospondin-4 （THBS4）在癌症的发生和发展中起重要作用。然而，它们在胃癌（GC）中作用的遗传证据缺乏。本研究旨在探讨中国东南部人群中THBS2/THBS4多态性与胃癌风险和临床病理特征的关系。采用基质辅助激光解吸/电离飞行时间质谱法对761例GC病例和739例对照进行了THBS2和THBS4 8个标记snp的基因分型。采用实时荧光定量PCR技术研究了82例胃癌组织和小鼠胃组织中THBS2/THBS4 mRNA的表达。我们发现THBS2和THBS4在小鼠胃中都大量表达。人胃组织中THBS4 mRNA表达与肿瘤大小（P= 0.002）和肿瘤淋巴结转移（TNM）相关（P= 0.010）， THBS2 mRNA表达与TNM相关（P= 0.010）。rs77878919AG基因型患者更易发生弥漫性胃癌。THBS4 snp （rs77878919和rs7736549）对不良预后（TNM）风险有一定的累积影响，携带这两种不利基因型的患者的风险最高。此外，携带THBS4 rs10474606变异纯合AA的个体具有适度降低的GC风险。我们得出结论，THBS2/THBS4可能在GC中发挥重要作用，这得到了GC中mRNA过表达和THBS2/THBS4多态性与GC的适度关联的证据的支持。这些结果可能有助于胃癌的风险评估和预后预测。
Thrombospondin-2 (THBS2) and Thrombospondin-4 (THBS4) play an important role in cancer development and progression. However, genetic evidence for their roles in gastric cancer (GC) is lacking. The aim of this study was to explore the association of THBS2/THBS4 polymorphisms with risk and clinicopathological features of GC in a Southeast Chinese population. Eight tagging SNPs in THBS2 and THBS4 were genotyped in 761 GC cases and 739 controls from Chinese case control sets using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. THBS2/THBS4 mRNA expression was studied in 82 human GC tumors and in mouse stomach tissues by real-time PCR. We found that both THBS2 and THBS4 were abundantly expressed in mouse stomach. THBS4 mRNA expression in human stomach was associated with tumor size (P= 0.002) and tumor-node-metastasis (TNM) (P= 0.010), and THBS2 mRNA expression was associated with the TNM (P= 0.010). Patients with the rs77878919AG genotype were more prone to developing diffuse-type GC. THBS4 SNPs (rs77878919 and rs7736549) had a modest cumulative effect on the risk of poor prognosis (TNM), with that risk in the highest trend for patients carrying both these unfavorable genotypes. In addition, individuals carrying the THBS4 rs10474606 variant homozygous AA had a modest reduced GC risk. We conclude that THBS2/ THBS4 may be functional in playing important role in GC, which was supported by the evidence of the mRNA overexpression in GC and the modest associations of THBS2/THBS4 polymorphisms to GC. These findings might be useful for risk assessment and prognosis prediction of GC.