Abstract
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, p=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.
Highlights
Gastric cancer (GC) ranks fifth in incidence rate of all cancers and is the fourth leading cause of cancer-related deaths among all human cancers in both sexes worldwide [1].Over 1,000,000 new cases of GC and an estimated 783,000 deaths occurred globally in 2018 [2]. e highest GC incidence and mortality rates were found in East Asia [3], ranking second (13.5%) for males and fifth (7.1%) for females among the most commonly diagnosed cancers in Chinese people in 2018 [4]
Written permission was obtained from all participants, and the study was approved by the Institutional Review Board of the Air Force Military Medical University (Xi’an, China). e procedures were performed according to the approved guidelines and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards
Discussion e associations of Gap junction protein alpha 1 (GJA1) rs2071165 and Secretory carrier membrane protein 1 (SCAMP1) rs4530741 A > C and rs6874309 T > A polymorphisms with GC risk and prognosis were investigated in this study. e GJA1 gene rs2071165 AA/AG genotype significantly increased the risk of GC in the female Chinese population, which indicated that GJA1polymorphisms may contribute to GC susceptibility in females
Summary
Gastric cancer (GC) ranks fifth in incidence rate of all cancers and is the fourth leading cause of cancer-related deaths among all human cancers in both sexes worldwide [1].Over 1,000,000 new cases of GC and an estimated 783,000 deaths occurred globally in 2018 [2]. e highest GC incidence and mortality rates were found in East Asia [3], ranking second (13.5%) for males and fifth (7.1%) for females among the most commonly diagnosed cancers in Chinese people in 2018 [4]. E highest GC incidence and mortality rates were found in East Asia [3], ranking second (13.5%) for males and fifth (7.1%) for females among the most commonly diagnosed cancers in Chinese people in 2018 [4]. GC is a multifactorial disease resulting from both environmental and genetic factors. Previous studies have shown that genetic factors, lifestyle conditions, and environmental factors play important roles in the development of GC [5]. Hundreds of casecontrol studies have examined candidate polymorphisms in relation to GC, there is still insufficient evidence for genetic differences contributing to the different incidence rates of GC between males and females
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