Association of Apolipoprotein A2 Isoform Index with Demographic, Behavioral, and Clinical Risk Factors for Pancreatic Ductal Adenocarcinoma in a Single-Center Observational Study: Prelude to a Pancreatic Cancer Screening Algorithm?

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality rates therefore early diagnosis and treatment is essential in reducing mortality. Blood tests that can identify high-risk individuals is an unmet medical need. Methods: In this pilot observational study, remnant samples from routine clinical lab orders were tested on 265 patients presenting with abdominal pain and/or presence of pancreatitis, pancreatic cyst, gall stones, abdominal infections, hepatic cirrhosis/hepatitis, non-pancreatic cancer, or pre-, new onset and uncontrolled diabetes. Serum apolipoprotein A2 isoforms, a novel tumor marker, and carbohydrate antigen (CA) 19-9 were correlated to 3 demographic, 4 behavioral and 9 clinical risk factors associated with PDAC. Results: In a univariate analysis using tumor markers as a continuous variable, males, alcohol, smoking, opioid use, pancreatitis, pancreatic cyst and hepatic cirrhosis/hepatitis were associated with an abnormal apoA2 isoforms. In a multivariate analysis, all remained significant except for males and opioid use. CA19-9 was associated with smoking, obesity, pancreatic cyst, cirrhosis/hepatitis, non-pancreatic cancer, and pre- and uncontrolled diabetes. After multivariate analysis, cirrhosis/hepatitis, non-pancreatic cancer and prediabetes remained significant. When categorizing marker data using pre-established cutoffs, patients with abnormal apoA2 had 4.4 risk factors vs. 3.2 with normal apoA2 )< 0.0001). No difference between normal and abnormal results were observed for CA19-9. Conclusions: Correlating known PDAC risk factors, apoA2 isoforms and CA19-9 were associated with different factors, suggesting thereby providing independent information on risk. This may justify apoA2 isoforms as part of an algorithm with CA19-9 for cancer screening, particularly for high-risk individuals (e.g. genetic risk).