Risk factors for early-onset pancreatic ductal adenocarcinoma: A systematic literature review

Background: Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in population exposures and lifestyles. Patients and methods: We conducted a PRISMA-standard systematic literature review to identify non-heritable risk factors for early-onset pancreatic ductal adenocarcinoma (PDAC) (PROSPERO number: CRD42022299397). Systematic searches of MEDLINE and Embase bibliographic databases were performed (January 2022), and publications were screened against predetermined eligibility criteria; data were extracted using standardised data fields. The STROBE checklist was used to assess the completeness of reporting as a proxy for publication quality. Data were categorised by risk factor and analysed descriptively. Results: In total, 24 publications were included. All publications reported observational study data; thresholds for age group comparisons ranged between 40 and 65 years. Lifestyle factors investigated included smoking, alcohol consumption, obesity, physical inactivity, meat intake, socioeconomic status and geographical residence. Clinical factors investigated included pancreatitis, diabetes/insulin resistance, prior cancer and cancer stage at diagnosis, hepatitis B infection, metabolic syndrome and long-term proton pump inhibitor exposure. Publication STROBE scores were 6-21 (maximum, 22). Eight studies reported results adjusted for confounders. Potential nonheritable risk factors for early-onset PDAC that warrant further investigation included smoking, alcohol consumption, pancreatitis and hepatitis B infection. Conclusion: Evidence for non-heritable risk factors for early-onset PDAC is heterogeneous, but four factors were identified that might aid the identification of at-risk individuals who may benefit from screening and risk reduction strategies.