Abstract
Small intestinal adenocarcinomas (SIAs) are associated with predisposing conditions, including inflammatory bowel disease (IBD) and celiac disease, but also genetic syndromes such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). This nationwide cohort study investigated the incidence of genetic and non-genetic predisposing conditions in SIA and their influence on tumor characteristics and clinical features. Data were obtained from the Netherlands Cancer Registry. The incidence, characteristics, and clinical features per predisposing condition were analyzed in 2697 SIA patients diagnosed from 1999 through 2019. Of all SIA patients, 5.6% were known to have a genetic predisposing syndrome, of whom 4.0% had LS and 1.6% had a polyposis syndrome. In addition, 6.8% of SIA patients had a non-genetic predisposing condition: 3.9% IBD and 2.9% celiac disease. SIAs of patients with such predisposing syndromes or conditions were diagnosed at a younger age and earlier stage and affected the duodenum less often as compared to sporadic SIA patients. Both genetic and non-genetic predisposing conditions were associated with significantly better overall survival (OS) compared to sporadic SIA: sporadic SIA (median OS: 13.0 months, 95% CI: 11.8-14.2), LS (213.1 months, 99.3-NA), polyposis syndromes (61.3 months, 19.7-NA), IBD (29.5 months, 20.3-69.8), and celiac disease (50.4 months, 24.6-124.7). This nationwide cohort study shows significant differences between SIA with and without predisposing conditions and highlights the need for research on underlying molecular mechanisms to improve outcomes of SIA patients.