• Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
• Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

BACKGROUND: Chemoprevention of cancer with aspirin is controversial as a primary prevention strategy. We sought to investigate the association between aspirin frequency and risk of lung cancer in The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

METHODS: Using data from 101,722 participants in PLCO, we used a Cox regression model coupling with propensity score to detect the association between aspirin frequency and lung cancer risk.

RESULTS: High-frequency aspirin use significantly increased risk of lung cancer by 28% compared to no use (HR =1.28; 95% CI, 1.14-1.45; P=3.37×10^-5), especially for current smoker (HR =1.30; 95% CI, 1.07-1.57; P=6.82×10^-3). However, the increased lung cancer risk due to high-frequency aspirin use significantly decreased with increasing bodyweight (HR_interaction =0.96; 95% CI, 0.94-0.99; P=1.26×10^-2). Further, for participants with bodyweight <80 kg, high-frequency aspirin use showed an elevated risk at <76 years of age (HR_age<76 =1.47; 95% CI, 1.25-1.73; P=3.81×10^-6). Our study used propensity score under various confounding and stratification analyses by cardio-cerebrovascular status, which all presented similar evidences.

CONCLUSIONS: High-frequency aspirin use is associated with the increased risk of lung cancer. Current smoker or people with age <76 years and bodyweight <80 kg should be more cautious to high-frequency aspirin use for lung cancer chemoprevention. This study provides a new insight for lung cancer chemoprevention.