Gastric cancer risk rises in familial adenomatous polyposis

Patients with familial adenomatous polyposis (FAP) in the Netherlands have a 12-fold higher risk of gastric cancer than the general population, and since 2020 gastric cancer has become the most frequently diagnosed malignancy in this population, according to a nationwide cohort study published in Gastroenterology.

Dutch investigators led by senior author Evelien Dekker, MD, PhD, of the Department of Gastroenterology and Hepatology at Amsterdam University Medical Center analyzed 1,230 patients with FAP identified through the Netherlands Foundation for Detection of Hereditary Tumors registry and the Dutch Nationwide Pathology Databank from 1975 to 2024. Median age at last follow-up was 51 years (IQR, 39-64), and 48% were women. A pathogenic APC variant was confirmed in 92.5%.

Overall, 388 patients (31.5%) developed 461 cancers. The most common were colon (n = 129), rectal (n = 77), duodenal (n = 31) and gastric (n = 28). Nearly half of colorectal cancers (49.5%) were index cancers diagnosed at initial FAP presentation.

Using Fine and Gray competing risk models, cumulative incidence at age 70 was 13.2% for colon cancer and 9.8% for rectal cancer. At age 80, estimates were 15.3% and 11.5%, respectively. Duodenal cancer incidence reached 4.4% at age 70 and 6.2% at age 80; gastric cancer incidence was 4.3% and 4.6%, respectively.

Gastric cancer cases increased from four (0.4%) in 2006-2015 to 18 (2.1%) in 2016-2024 (P < .01). Since 2020, 11 gastric cancers were diagnosed compared with four colon cancers.

Standardized incidence ratios showed significantly elevated risks for gastric cancer (SIR, 12.02), colorectal cancer (SIR, 14.22), duodenal cancer (SIR, 277.28), ampullary cancer (SIR, 113.85), small-bowel cancer (SIR, 122.03), hepatoblastoma (SIR, 747.52) and hepatocellular carcinoma (SIR, 5.43). Extraintestinal risks were also increased for thyroid (SIR, 17.35), gynecologic (SIR, 2.27) and central nervous system cancers (SIR, 3.79).

Surveillance-detected colorectal cancers were more often stage I and less often stage IV than in the general population, whereas 43% of gastric cancers were diagnosed at stage IV.

During follow-up, 262 deaths occurred vs 134 expected (SMR, 1.96). The researchers noted certain limitations of the study, including the retrospective registry design and lack of detailed surveillance data.

The authors reported having no relevant financial disclosures.