New research has found a promising link between exposure to leukotriene inhibitors and a reduction in the risk of lung cancer.

Investigators at the University of South Carolina concluded that U.S. veterans who used the common asthma drug had a 22% reduced risk of lung cancer than did those who were not exposed to the agent.

Reporting online in Pulmonary Pharmacology & Therapeutics, the researchers noted that leukotriene inhibition has been previously found to suppress tumor growth across a variety of cancer cells in both in vitro and in vivo models. Indeed, a recent Taiwanese database analysis demonstrated a significant protective effect of the leukotriene inhibitor montelukast for lung cancer prevention. Subsequently, research in a mouse model revealed that montelukast induced lung cancer cell death. 

"With pre-clinical and clinical data demonstrating an effect of leukotriene inhibition on lung cancer, we sought to demonstrate a unique integration of large-scale patient level longitudinal data complimenting previously published biomedical research,” the authors wrote.

To help explore the relationship between leukotriene inhibition and incident lung cancer in a national cohort of US veterans with asthma, the researchers extracted data from the VA Informatics and Computing Infrastructure (VINCI), a database that comprises inpatient, outpatient, and pharmacy claims from the Department of Veteran Affairs (VA). All individuals presenting between October 1999 and September 30, 2020 were included. A variety of statistical techniques were used to examine the association between leukotriene medication use and the risk of lung cancer. 

In total, 558,466 patients met study criteria, comprising 23,730 patients with leukotriene exposure and 534,736 patients with no such medication use. The majority of patients in each cohort were White, middle-aged males with a body mass index >30. Interestingly, unexposed individuals in the cohort had a higher average Charlson comorbidity index than did those who were exposed to the medication, along with higher percentages of hypercholesterolemia, hypertension, smoking, and alcohol use. 

According to lead author S. Scott Sutton, PharmD, Professor and Chair of the College of Pharmacy in the Department of Clinical Pharmacy and Outcomes Sciences at the University of South Carolina, individuals who were exposed to leukotriene inhibition demonstrated a reduced risk of lung cancer. Indeed, the risk was decreased by 17% in the unmatched analysis (HR = 0.830) and by 22% in the matched analysis (HR = 0.778). And while falsification testing suggested no evidence of selection bias, the investigators pointed out that residual confounding cannot be ruled out since treatment was not randomized.

Yet despite such potential shortcomings, the researchers nevertheless seemed encouraged by the findings from what they called the first study to demonstrate the potential chemoprevention role of targeting leukotrienes in lung cancer. 

“The pre-clinical data on leukotriene inhibition and lung cancer combined with our database analysis provide intriguing evidence warranting further research into the relationship between leukotrienes and lung cancer,” the authors wrote.