Gastric cancer (GC) has emerged as one of the major concerns in familial adenomatous polyposis (FAP) nowadays. To improve prevention, it is essential to identify which FAP patients are at increased risk of GC. We aimed to determine clinicopathological factors associated with GC in FAP.

We conducted a case-control study including FAP patients with histologically confirmed GC identified through the nationwide Netherlands Foundation for Detection of Hereditary Tumours (StOET). Controls were FAP patients who underwent at least one surveillance esophagogastroduodenoscopy (EGD) at a tertiary expert center. Descriptive statistics were used to summarize clinical characteristics and potential associations with GC were evaluated using univariate logistic regression.

A total of 28 FAP patients with GC and 188 controls without GC were identified. The median age at GC diagnosis was 56 years (IQR 49–63), compared to 45 years (IQR 35–58) at last surveillance endoscopy in controls (p < 0.01). Carpeting fundic gland polyposis (71% vs. 27%; OR 13.8, p < .01) and prior gastric dysplasia (71% vs. 27%; OR 6.7, p < .01) were strongly associated with GC, particularly when located proximal to the angulus (OR 7.6, p < .01). In contrast, Spigelman stage did not differ between cases and controls (OR 0.91; p = .82). GC clustered in three pedigrees (seven affected members). Of the 28 cancers, 23 (82%) were located proximal to the angulus and 5 (18%) in the antrum. Among the proximal cancers, five were initially detected at stage I and treated curatively. Three of these progressed to metastatic disease within one year, while two patients (with a junction tumor and a stage I corpus carcinoma) remain cancer-free at 5 and 2 years of follow-up, respectively. All other proximal cancers were stage IV at diagnosis. Among the antral cancers, two patients with stage I disease remain cancer-free at 19 and 5 years after curative treatment, while the remaining cases deceased within two years.

GC in FAP predominantly occurs in the proximal stomach and is strongly associated with carpeting fundic gland polyposis and prior gastric dysplasia, whereas Spigelman stage was not predictive. Surveillance in patients with these clinical characteristics should primarily aim at early detection and removal of premalignant dysplastic lesions.