Yuan Lijuan, Yang Ping, Wei Gang, Lu Jianguo, Yang Zhengyu, Yang Lin, Peng Shujia, He Xianli, Bao Guoqiang
Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an 710032, China.
J Oncol. 2021 May 19;2021:5556303. doi: 10.1155/2021/5556303. eCollection 2021.
Gastric cancer (GC) is one of the most common malignancies, and its incidence rates vary widely between men and women. Previous studies have suggested that connexin 43 (Cx43, encoded by gap junction protein alpha 1 (GJA1)) and secretory carrier membrane protein 1 (SCAMP1) are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated. A total of three single-nucleotide polymorphisms among 681GC patients and 756 controls were tested using the Agena MassARRAY RS1000 system, including GJA1 rs2071165, SCAMP1 rs4530741, and SCAMP1 rs6874309. The strength of the association with GC risk was assessed by the odds ratios (ORs) and 95% confidence intervals (CIs) generated from the logistic regression model. Kaplan-Meier curve, long-rank tests, and a multivariate Cox proportional hazard model were used for prognosis analysis. The expression of GJA1 was assessed by immunohistochemistry. The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (OR = 1.55, 95% CI = 1.03-2.32, =0.034). Furthermore, the risk effect of GJA1 rs2071165 was more evident in the subgroups of female patients with GC, stratified by age, clinical stage, tumor size, and recurrence/metastasis. However, no obvious differences in Cx43 expression in GC tissues were observed between males and females. Furthermore, no significant association between SCAMP1 rs4530741 and rs6874309 polymorphisms and GC risk or prognosis was observed. In conclusion, this study suggests for the first time that the GJA1 rs2071165 polymorphism is associated with increased GC risk in females, revealing a potential new clinical marker for assessing GC risk in females.
胃癌（GC）是最常见的恶性肿瘤之一，其发病率在男性和女性之间差异很大。先前的研究表明，连接蛋白43（Cx43，由间隙连接蛋白α1（GJA1）编码）和分泌载体膜蛋白1（SCAMP1）是肿瘤中的关键功能蛋白。在此，评估了GJA1和SCAMP1基因多态性与GC易感性和预后之间的关联。使用Agena MassARRAY RS1000系统对681例GC患者和756例对照中的总共三个单核苷酸多态性进行了检测，包括GJA1 rs2071165、SCAMP1 rs4530741和SCAMP1 rs6874309。通过逻辑回归模型生成的比值比（OR）和95%置信区间（CI）评估与GC风险的关联强度。采用Kaplan-Meier曲线、长秩检验和多变量Cox比例风险模型进行预后分析。通过免疫组织化学评估GJA1的表达。GJA1 rs2071165 AA/AG基因型显著增加了中国女性人群患GC的风险（OR = 1.55，95% CI = 1.03 - 2.32，P = 0.034）。此外，GJA1 rs2071165的风险效应在按年龄、临床分期、肿瘤大小和复发/转移分层的女性GC患者亚组中更为明显。然而，在男性和女性的GC组织中未观察到Cx43表达的明显差异。此外，未观察到SCAMP1 rs4530741和rs6874309基因多态性与GC风险或预后之间存在显著关联。总之，本研究首次表明GJA1 rs2071165多态性与女性GC风险增加相关，揭示了一种潜在的评估女性GC风险的新临床标志物。
