The factors that raise the risk of pancreatic cancer are usually divided into those that cannot be changed and those that can. None of them is a single decisive cause, and most people who develop the disease have none of the rare inherited conditions.
Fixed risk factors
- Advanced age
- Male sex
- African American race
- A family history of pancreatic cancer
Modifiable risk factors
Smoking is the most important modifiable factor. Smokers have a relative risk about 1.7 times that of the general population, and the relation is dose-dependent, so the risk rises with the amount and duration smoked. Smoking is estimated to be at least one causative agent in more than 20–25% of cases. Alcohol use and obesity are also associated with the disease.
Diabetes has a more complicated relationship with pancreatic cancer than it first appears, because the direction of cause runs both ways. Long-standing diabetes raises the risk modestly, with a relative risk of roughly 1.7 to 1.9. A new diagnosis of diabetes, by contrast, is associated with a much higher risk — an 8-fold increase in the first 3 years — but this usually reflects the tumour rather than causing it: pancreatic cancer itself disturbs glucose metabolism, so new-onset diabetes can be an early clue to the cancer rather than a risk factor for it. About half of patients with pancreatic cancer already have diabetes when the cancer is found, and about 40% developed the diabetes in the 3 years beforehand.
Concern was raised that the incretin-based anti-diabetic drugs, the GLP-1 receptor agonists and DPP-4 inhibitors, might increase the risk of pancreatic cancer. Meta-analyses of randomised trials have not confirmed an association. Observational data suggest that metformin may be associated with a lower risk, but this has not been established as a protective effect.