Genomic and clinical parallels between US and Japanese gastric cancers: a propensity score-matched cohort study

Introduction: Gastric cancer incidence, risk factors, and survival outcomes differ significantly between Japan and the United States. These disparities have led to the belief that gastric cancer represents biologically distinct diseases across regions. However, direct genomic comparisons of tumours from these populations have not been performed. The aim of this study was to compare the genomic and clinical characteristics of gastric cancers in patients from the US and Japan following curative-intent resection. Methods: A retrospective cohort study of patients who underwent curative-intent gastrectomy between 2010 and 2019 at Memorial Sloan Kettering (MSK, n = 142) and Fujita Health University (FHU, n = 108), with ≥5 years of follow-up, was conducted. Tumour samples underwent targeted sequencing. Clinical and genomic data were compared between unmatched and propensity score-matched (PSM) cohorts, matched by age, sex, clinical T/N-category, and tumour location (n = 58 each). Results: Commonly altered genes included TP53 (60%), ARID1A (17%), ERBB2 (14%), CCNE1 (13%), and KRAS (12%). MSK tumours showed higher rates of microsatellite instability (MSI-high; 22.4% versus 5.2%, P = 0.013) and KMT2D mutations (18% versus 5%, P < 0.05). Otherwise, gene- and pathway-level alterations were similar across unmatched, microsatellite stable only, and PSM cohorts. Five-year overall survival in PSM cohorts was comparable (MSK 60% versus FHU 69.4%, P = 0.548). Peritoneal recurrence was more common in the MSK cohort (47% versus 34%), but recurrence patterns were not associated with distinct genomic profiles. Conclusion: After adjustment for clinical covariates, US and Japanese gastric cancers exhibit comparable genomic landscapes and survival, supporting the relevance of clinical trial data across geographic settings.