Pancreatic cancer is associated with medication changes prior to clinical diagnosis

Yin Zhang; Qiao-Li Wang; Chen Yuan; Alice A Lee; Ana Babic; Kimmie Ng; Kimberly Perez; Jonathan A Nowak; Jesper Lagergren; Meir J Stampfer; Edward L Giovannucci; Chris Sander; Michael H Rosenthal; Peter Kraft; Brian M Wolpin

doi:10.1038/s41467-023-38088-2

Pancreatic cancer is associated with medication changes prior to clinical diagnosis

Nat Commun. 2023 Apr 28;14(1):2437. doi: 10.1038/s41467-023-38088-2.

Authors

Yin Zhang^{1

2}, Qiao-Li Wang^{1

3}, Chen Yuan¹, Alice A Lee⁴, Ana Babic¹, Kimmie Ng¹, Kimberly Perez¹, Jonathan A Nowak⁵, Jesper Lagergren^{6

7}, Meir J Stampfer^{2

8

9}, Edward L Giovannucci^{2

9}, Chris Sander^{10

11

12}, Michael H Rosenthal¹³, Peter Kraft^{9

14}, Brian M Wolpin¹⁵

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
² Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
³ Department of Clinical Science, Intervention and Technology, Karolinka Institutet, Stockholm, Sweden.
⁴ Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
⁷ School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
⁸ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
¹⁰ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
¹¹ Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
¹² Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹³ Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. brian_wolpin@dfci.harvard.edu.

Abstract

Patients with pancreatic ductal adenocarcinoma (PDAC) commonly develop symptoms and signs in the 1-2 years before diagnosis that can result in changes to medications. We investigate recent medication changes and PDAC diagnosis in Nurses' Health Study (NHS; females) and Health Professionals Follow-up Study (HPFS; males), including up to 148,973 U.S. participants followed for 2,994,057 person-years and 991 incident PDAC cases. Here we show recent initiation of antidiabetic (NHS) or anticoagulant (NHS, HFS) medications and cessation of antihypertensive medications (NHS, HPFS) are associated with pancreatic cancer diagnosis in the next 2 years. Two-year PDAC risk increases as number of relevant medication changes increases (P-trend <1 × 10^-5), with participants who recently start antidiabetic and stop antihypertensive medications having multivariable-adjusted hazard ratio of 4.86 (95%CI, 1.74-13.6). These changes are not associated with diagnosis of other digestive system cancers. Recent medication changes should be considered as candidate features in multi-factor risk models for PDAC, though they are not causally implicated in development of PDAC.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antihypertensive Agents / therapeutic use
Carcinoma, Pancreatic Ductal* / diagnosis
Carcinoma, Pancreatic Ductal* / drug therapy
Female
Follow-Up Studies
Humans
Hypoglycemic Agents / therapeutic use
Male
Pancreatic Neoplasms* / diagnosis
Pancreatic Neoplasms* / pathology

Substances

Antihypertensive Agents
Hypoglycemic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding