Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma
(PDAC) cases, and the etiology of this form is poorly understood. It is not clear
if established PDAC risk factors have the same relevance for younger patients. This
study aims to identify genetic and non-genetic risk factors specific to EOPC.A genome-wide
association study was performed, analysing 912 EOPC cases and 10 222 controls, divided
into discovery and replication phases. Furthermore, the associations between a polygenic
risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were
also assessed.Six novel SNPs were associated with EOPC risk in the discovery phase,
but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk.
The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69-5.04, P =
1.44 × 10-4). For diabetes, the corresponding OR was 14.95 (95% CI 3.41-65.50, P =
3.58 × 10-4).In conclusion, we did not identify novel genetic variants associated
specifically with EOPC, and we found that established PDAC risk variants do not have
a strong age-dependent effect. Furthermore, we add to the evidence pointing to the
role of smoking and diabetes in EOPC.
