Long-Term Antibiotic Exposure May Increase Lung Cancer Risk

Cumulative days of antibiotic use and number of antibiotic drug class exposures are associated with lung cancer risk, according to results of a study published in the Journal of Infection and Public Health.

There is evidence to suggest that gut microbiota dysbiosis may increase lung cancer risk; however, the role of long-term antibiotic exposure on the risk for lung cancer has not been fully elucidated.

In a longitudinal retrospective study, researchers analyzed data sourced from the Korean National Health Insurance Services database to evaluate the relationship between long-term antibiotic use and the risk for lung cancer. Antibiotic use occurring between 2002 and 2006 was evaluated in relation to lung cancer incidence occurring between 2007 and 2019 among a population of 6,214,926 patients. The association between antibiotic use and lung cancer risk was assessed via multivariable Cox proportional hazards regression.

Patients were divided into 6 groups based on cumulative days of antibiotic use between 2007 and 2019. The 6 groups included patients with no antibiotic exposure (n=327,314), and those with 1 to 14 (n=1,011,786), 15 to 59 (n=1,479,312), 60 to 179 (n=1,501,561), 180 to 364 (n=818,532), and 365 days and more of exposure (n=1,076,430).

Overall, the mean patient age ranged between 53.65 and 56.55 years, and 48.07% to 65.79% were men. Patients with the longest duration of antibiotic use were more likely to have higher BMIs, higher total cholesterol levels, and more comorbidities (all P <.001).

The researchers found a clear duration-dependent relationship between antibiotic use and lung cancer incidence in all models (all P <.001). In the fully adjusted model, lung cancer risk was increased among patients with cumulative antibiotic use rates of 365 days and more compared with those with no exposure (adjusted hazard ratio [aHR], 1.21; 95% CI, 1.16-1.26). Similar findings were noted among patients with 180 to 364 (aHR, 1.14; 95% CI, 1.09-1.19), 60 to 179 (aHR, 1.09; 95% CI, 1.05-1.14), and 15 to 59 (aHR, 1.05; 95% CI, 1.01-1.09) cumulative days of antibiotic exposure (P <.001).

Further analysis was performed in which patients with 1 to 14 days of antibiotic exposure were used as the comparator group. Results showed that the highest risk for lung cancer was associated with antibiotic use for 365 days and longer (aHR, 1.21; 95% CI, 1.17-1.24), followed by antibiotic use for 180 to 364 (aHR, 1.12; 95% CI, 1.09-1.16), 60 to 179 (aHR, 1.08; 95% CI, 1.05-1.11), and 15 to 59 days (aHR, 1.03; 95% CI, 1.01-1.06).

Results indicating a significant association between greater antibiotic exposure and increased lung cancer risk were consistent in sensitivity analyses that incorporated wash-out periods, comorbidity exclusions, and variations in exposure or follow-up periods (all P <.001).

Significant subgroup interaction effects were observed for age and smoking status (both P <.001).

In addition, patients who were exposed to 5 or more antibiotic drug classes were at increased risk for lung cancer compared with those with no exposure (aHR, 1.15; 95% CI, 1.10-1.21; P <.001).

This study may have been limited by the retrospective design, the inability to confirm adherence to prescribed antibiotics, and the lack of data on lung cancer characteristics.

“[T]his nationally representative study is the first in Asia to provide real-world evidence of antibiotic exposure as a risk-enhancing factor for lung cancer,” the researchers concluded.