Introduction: An increase in the incidence of duodenal adenocarcinoma has been recently reported. However, little is known about the risk factors for duodenal adenocarcinoma, which are important for screening purposes. We, therefore, aimed to conduct a systematic review to identify risk factors for non-ampullary duodenal adenocarcinoma. Methods: A medical literature search was performed using electronic databases, including PubMed, Cochrane Library, Japan Medical Abstracts Society, and Web of Science. Studies that assessed the association between dietary habits, lifestyle behaviors, comorbidities, and non-ampullary duodenal adenocarcinoma were extracted. The Newcastle-Ottawa Scale was used to assess the risk of bias in individual studies, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the quality of evidence across studies included in this review. Results: Out of 1,244 screened articles, 10 were finally selected for qualitative synthesis. In the general population, no consistent risk factors were identified except for Helicobacter pylori positivity, which was considered a risk factor in 2 studies, but the quality of evidence was considered very low because of the high risk of bias. In patients with familial adenomatous polyposis (FAP), Spigelman stage IV at initial endoscopy was considered a consistent risk factor in 3 studies. Conclusions: There are currently limited data regarding risk factors for non-ampullary duodenal adenocarcinoma, and no conclusive risk factors were identified in the general population. However, in patients with FAP, Spigelman stage IV was identified as a consistent risk factor. Further studies are needed to improve diagnosis and support effective clinical management of this malignancy.
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