Pancreatic ductal adenocarcinoma (PDAC) is challenging to diagnose due to the frequently vague and late-presenting symptoms of this disease, often leading to late diagnosis. A greater understanding of the risk factors for PDAC would aid earlier diagnosis, increasing the likelihood of better outcomes for patients with PDAC.
While some clinical factors such as new-onset Type 2 diabetes have been associated with an increased risk of PDAC diagnosis, the sheer numbers of people affected by these risk factors (e.g. 200,000 new diagnoses of Type 2 diabetes per year in England) mean that screening would not be practical in this population. Further enrichment of people at higher PDAC risk would help to identify the population who could benefit most from screening.
A team of researchers from the University of Oxford led by Professor Julia Hippisley-Cox (Nuffield Department of Primary Care and Health Sciences) and Dr Shivan Sivakumar (Department of Oncology) have studied how PDAC risk factors vary over time leading up to a PDAC diagnosis. Using the QResearch population-level electronic healthcare database, the body mass index (BMI), blood-based markers, comorbidities and medication use of 28,137 people before their PDAC diagnosis were compared with these factors in 261,219 matched controls.
In a paper published in the journal Gut, the researchers found that the risk of PDAC increased with higher blood levels of glucose, liver function markers, white blood cells and platelets, while both very low and very high BMIs and blood haemaglobin levels were associated with increased PDAC risk.
Looking over time, BMI decreased and blood glucose increased gradually 2-3 years before a PDAC diagnosis, with more rapid changes in the 1-2 years prior to PDAC. By contrast, liver markers, white blood cells and platelets were reasonably stable in the 2-3 years before diagnosis but showed rapid increases ~1 year prior to diagnosis. The highest risk of PDAC was associated with a recent diagnosis of a pancreatic cyst, pancreatitis, Type 2 diabetes and starting on certain glucose-lowering and acid-regulating therapies.
This enhanced knowledge about how PDAC risk factors vary over time prior to diagnosis could be combined into future risk prediction tools to identify people at an increased PDAC risk. In the future, this population with higher risk level could then be targeted for further investigation to aid earlier PDAC diagnosis.