Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): a nested case–control study

Tan, Pui San; Garriga, Cesar; Clift, Ashley; Liao, Weiqi; Patone, Martina; Coupland, Carol; Bashford-Rogers, Rachael; Sivakumar, Shivan; Hippisley-Cox, Julia

Abstract

Objective Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk .

Design We performed a population-based nested case–control study of 28 137 PDAC cases and 261 219 matched-controls in England. We described the associations of biomarkers with risk of PDAC using fractional polynomials and 5-year time trends using joinpoint regression. Associations with comorbidities and medication use were evaluated using conditional logistic regression.

Results Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while following a U-shaped relationship for BMI and haemoglobin. Five-year trends showed biphasic BMI decrease and HbA1c increase prior to PDAC; early-gradual changes 2–3 years prior, followed by late-rapid changes 1–2 years prior. Liver markers and blood counts (white blood cell, platelets) showed monophasic rapid-increase approximately 1 year prior. Recent diagnosis of pancreatic cyst, pancreatitis, type 2 diabetes and initiation of certain glucose-lowering and acid-regulating therapies were associated with highest risk of PDAC.

Conclusion Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while followed a U-shaped relationship for BMI and haemoglobin. BMI and HbA1c derange biphasically approximately 3 years prior while liver markers and blood counts (white blood cell, platelets) derange monophasically approximately 1 year prior to PDAC. Profiling these in combination with their temporality could inform earlier PDAC diagnosis.

Citation

Tan, P. S., Garriga, C., Clift, A., Liao, W., Patone, M., Coupland, C., Bashford-Rogers, R., Sivakumar, S., & Hippisley-Cox, J. (2023). Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): a nested case–control study. Gut, 72(3), 512-521. https://doi.org/10.1136/gutjnl-2021-326522

• Journal Article Type: Article
• Acceptance Date: Jun 14, 2022
• Online Publication Date: Jun 27, 2022
• Publication Date: 2023-03
• Deposit Date: Jul 18, 2022
• Publicly Available Date: Jul 18, 2022
• Journal: Gut
• Print ISSN: 0017-5749
• Electronic ISSN: 1468-3288
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 72
• Issue: 3
• Pages: 512-521
• DOI: https://doi.org/10.1136/gutjnl-2021-326522
• Keywords: Gastroenterology
• Public URL: https://nottingham-repository.worktribe.com/output/9085133
• Publisher URL: https://gut.bmj.com/content/early/2022/06/27/gutjnl-2021-326522