Xiang Fenfen, Ni Zhenhua, Zhan Yueping, Xu Jian, Wu Rong, Kang Xiangdong
Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Central Lab, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Clin Lab Anal. 2018 Jan;32(1). doi: 10.1002/jcla.22182. Epub 2017 Mar 13.
A polymorphic variant allele (T-allele) in the 3'-UTR of prohibitin (C-to-T at nucleotide 729) was reported to be associated with an increased risk of breast cancer. However, the association between the 3'-UTR polymorphism of prohibitin and the susceptibility to gastric cancer remains unknown. Thus, we investigated the distribution of prohibitin genotypes in Chinese patients with gastric cancer and subsequently analyzed the association between the 3'-UTR polymorphism of prohibitin and the risk of gastric cancer in that population.
The distribution of 3'-UTR polymorphism of prohibitin in 82 gastric cancer patients was determined by sequencing and compared with that of 171 healthy controls. Luciferase reporter assay was used to investigate the effect of 3'-UTRs variant on PHB expression.
Our study discovered two major polymorphic sites in the 3'-UTR of prohibitin (C-to-T at nucleotide 729 and G to A at nucleotide 758). The C/T polymorphism at 729 site was not associated with the increased risk of gastric cancer (P=.961, OR=1.044, 95%CI: 0.187-5.818); however, G/A polymorphism at nucleotide 758 increased the risk of gastric cancer (P=.017, OR=1.923, 95%CI: 1.119-3.305). Luciferase reporter constructs containing the 758A allele showed higher luciferase activity compared with the wild-type allele, which indicated that 758 G>A in 3'-UTR increased PHB expression.
The G to A transition but not the C-to-T transition in the 3'-UTR of prohibitin was associated with an increased risk of gastric cancer in Chinese population.
据报道，抑制素3'-非翻译区（3'-UTR）中的一个多态性变异等位基因（T等位基因，核苷酸729处C突变为T）与乳腺癌风险增加相关。然而，抑制素3'-UTR多态性与胃癌易感性之间的关联尚不清楚。因此，我们调查了中国胃癌患者中抑制素基因型的分布，并随后分析了抑制素3'-UTR多态性与该人群胃癌风险之间的关联。
通过测序确定了82例胃癌患者中抑制素3'-UTR多态性的分布，并与171例健康对照进行比较。使用荧光素酶报告基因检测来研究3'-UTR变异对PHB表达的影响。
我们的研究在抑制素3'-UTR中发现了两个主要多态性位点（核苷酸729处C突变为T和核苷酸758处G突变为A）。729位点的C/T多态性与胃癌风险增加无关（P = 0.961，OR = 1.044，95%CI：0.187 - 5.818）；然而，核苷酸758处的G/A多态性增加了胃癌风险（P = 0.017，OR = 1.923，95%CI：1.119 - 3.305）。与野生型等位基因相比，含有758A等位基因的荧光素酶报告基因构建体显示出更高的荧光素酶活性，这表明3'-UTR中的758 G>A增加了PHB表达。
在中国人群中，抑制素3'-UTR中的G突变为A而非C突变为T与胃癌风险增加相关。
