Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival

Objectives: Early-onset pancreatic cancer (EOPC) – defined as pancreatic cancer diagnosed before the age of 50 years – is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival. Materials and Methods: Using PubMed and Medline, the following terms were searched and relevant citations assessed: “early onset pancreatic cancer,” “late onset pancreatic cancer,” “pancreatic cancer,” “pancreatic cancer genes,” and “pancreatic cancer targeted therapy.” Results: Mutations in CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC. Conclusions: Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management.