Incidence of Cancer in Patients With Familial Adenomatous Polyposis in the Netherlands: A Nationwide Cohort Study

Background & Aims: Patients with familial adenomatous polyposis (FAP) are at increased risk of several gastrointestinal and extraintestinal cancers. Although prophylactic surgery has reduced colorectal cancer (CRC) incidence, the lifetime incidence of other cancers has increased. This study assessed the cumulative risks in Dutch FAP patients over the past decades. Methods: This nationwide cohort study identified FAP patients from the Netherlands Foundation for Detection of Hereditary Tumors national registry and cross-referenced them with the Dutch Pathology Registry. Cumulative cancer incidences between 1975 and 2024 were estimated using the Fine and Gray competing risk method. Standardized incidence ratios (SIRs) were calculated relative to the general population for all cancer types. Results: A total of 1230 patients (48% women) with FAP were included, of whom 388 (32%) developed a total of 461 cancers. A pathogenic APC variant was identified in 1138 (93%) patients. The most frequently observed cancers were colon (n = 129), rectal (n = 77), duodenal (n = 31), and gastric (n = 28). Since 2020, the observed incidence of gastric cancer has risen to the most commonly diagnosed cancer. SIR analysis showed significantly increased risks for gastrointestinal cancers, including gastric cancer (SIR, 12.02; P < .01), duodenal cancer (SIR, 277.28; P < .01), ampullary cancer (SIR, 113.85; P < .01), CRC (SIR, 14.22; P < .01), small-bowel cancer (SIR, 122.03; P < .01), hepatoblastoma (SIR, 747.52; P < .01), and hepatocellular carcinoma (SIR, 5.43; P = .01). Among extraintestinal cancers, elevated risks were observed for thyroid cancer (SIR, 17.30; P < .01), gynecologic cancers (SIR, 2.27; P < .01), and central nervous system cancers (SIR, 3.79; P < .01). Conclusions: Despite developments in preventive treatments, individuals with FAP remain at increased risk for multiple cancers, underscoring the need for improved screening and surveillance strategies.