Aspirin, Statins, Non-aspirin NSAIDs, Metformin, and the Risk of Biliary Cancer: A Swedish Population-Based Cohort Study.

Abstract

BACKGROUND:

Chemoprevention for biliary tract cancers (BTC), which comprise intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer, is controversial. We examined associations between low-dose aspirin, statins, NSAIDs, and metformin with BTC risk.

METHODS:

We used a population-based cohort of 5.7 million persons over age 18 without personal history of cancer (except nonmelanoma skin cancer), receiving at least one commonly prescribed drug between July 1, 2005, and December 31, 2012, from the Swedish Prescribed Drug Registry. Hazard ratios (HR) were calculated using age-scaled multivariable-adjusted Cox models.

RESULTS:

2,160 individuals developed BTC. Low-dose aspirin was not associated with BTC risk [HR, 0.93; 95% confidence interval (CI), 0.81-1.07], iCCA (HR, 1.21; 95% CI, 0.93-1.57), eCCA (HR, 0.80; 95% CI, 0.60-1.07), or gallbladder cancer (HR, 0.87; 95% CI, 0.71-1.06). Statins were associated with lower risk of BTC (HR, 0.66; 95% CI, 0.56-0.78), iCCA (HR, 0.69; 95% CI, 0.50-0.95), eCCA (HR 0.54; 95% CI, 0.38-0.76), and gallbladder cancer (HR, 0.72; 95% CI, 0.57-0.91). For all BTC subtypes, combined low-dose aspirin and statins were not associated with lower risk than statins alone. NSAIDs were associated with higher risk of BTC and its subtypes. Metformin was not associated with BTC risk (HR, 0.98; 95% CI, 0.82-1.18), iCCA (HR, 1.06; 95% CI, 0.77-1.48), eCCA (HR, 1.15; 95% CI, 0.82-1.61), or gallbladder cancer (HR, 0.84; 95% CI, 0.63-1.11).

CONCLUSIONS:

Statins were associated with a decreased risk of BTC and its subtypes. Low-dose aspirin alone was not associated with a decreased risk, and use of both was not associated with further decrease in risk beyond statins alone.

IMPACT:

Statins were most consistently associated with a decreased risk of BTC and its subtypes.

• Authors: Lorena Marcano-Bonilla, Cathy D Schleck, William S Harmsen, Omid Sadr-Azodi, Mitesh J Borad, Tushar Patel, Gloria M Petersen, Terry M Therneau, Lewis R Roberts, Nele Brusselaers
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 31 Issue 4 Pg. 804-810 (04 01 2022) ISSN: 1538-7755 [Electronic] United States
• PMID: 35086822 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Metformin
• Aspirin

Topics

• Adolescent
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Aspirin (therapeutic use)
• Bile Duct Neoplasms (epidemiology, prevention & control)
• Bile Ducts, Intrahepatic (pathology)
• Biliary Tract Neoplasms (epidemiology)
• Cohort Studies
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects)
• Metformin (therapeutic use)
• Risk Factors
• Sweden (epidemiology)