GJA1 rs2071165 A>G Variant Increased Gastric Cancer Risk in Females of Northwest China: A Case-control Study

Abstract Background: 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 Cx43 and SCAMP1 are key functional proteins in tumors. Herein, the association between GJA1 and SCAMP1 polymorphisms and GC susceptibility and prognosis was evaluated.Methods: A total of three SNPs among 681 GC patients and 756 controls were tested using the Agena Mass ARRAY RS1000 system including GJA1 rs2071165, SCAMP1 rs4530741, and rs6874309. The strength of the association with cancer risk was assessed by the odds ratios and 95% confidence intervals 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.Results: The GJA1 rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population (odds ratio [OR] =1.55, 95% confidence interval, 95%CI] = 1.03–2.32, p = 0.034). Furthermore, the risk effect of 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 rs4530741 and rs6874309 polymorphisms in SCAMP1 and GC risk or prognosis was observed. Conclusion: In conclusion, this study suggests that GJA1 rs2071165 polymorphisms are associated with increased GC risk in females for the first time, which showed a potential new clinical marker for assessing GC risk in females.