Abstract
BACKGROUND: This study aims to investigate the differences in postoperative prognosis associated with the single nucleotide polymorphism (SNP) rs2228226 (G > C) in gastric adenocarcinoma (GAC) patients. METHODS: This study enrolled 661 patients with locally advanced (pT4a) GAC after surgery. DNA was extracted from their tissues and genotyped for rs2228226 using a MassARRAY Analyzer. Based on the patients' clinical and pathological information, a multifactorial Cox regression analysis was performed to assess the correlation between rs2228226 and the clinical prognosis of pT4a GAC patients. Survival differences among patients who received postoperative chemotherapy were also examined according to rs2228226. RESULTS: After excluding patients with distant metastasis, loss to follow-up, and those not meeting the inclusion criteria, a total of 463 patients with complete data were included. The rs2228226 genotype distribution was as follows: C/C = 57 (12.3%), G/C = 200 (43.2%), and G/G = 206 (44.5%). Patients with the C/C genotype had significantly shorter disease-free survival (DFS = 12 months) and overall survival (OS = 27 months) compared to those with the G/C or G/G genotype (DFS = 19 months, log-rank P = 0.003; OS = 35 months, log-rank P = 0.002). Further analysis of patients receiving chemotherapy identified the C/C genotype, advanced age, lymph node metastasis, degree of differentiation, and failure to achieve R0 resection as independent risk factors for tumor recurrence and metastasis (P < 0.05). The C/C genotype, lymph node metastasis, and tumor recurrence and metastasis were independent risk factors for mortality (P < 0.05). CONCLUSIONS: In pT4a GAC patients undergoing postoperative chemotherapy, the C/C genotype at rs2228226 is an independent risk factor for tumor recurrence, metastasis, and death. The rs2228226 (G > C) polymorphism may serve as a potential biomarker for predicting prognosis after chemotherapy in GAC.