Based on these findings, we hypothesize that the hypoxic microenvironment in pancreatic cancer activates the TGF-β1/Smad signaling pathway via HIF-1α, thereby synergistically promoting the expression of ECM proteins (e.g., collagen I/III/V) and exacerbating tumor invasion and stromal fibrosis. This evidence concerns the gene HIF1A and familial pancreatic carcinoma.