Dynamic impact of change of high-density lipoprotein cholesterol on lung cancer risk

The effect modification of high-density lipoprotein cholesterol (HDL-C) on lung cancer risk has been rarely explored, and the impact of HDL-C changes remains unreported; therefore, we investigated these associations. Using data from the Korean National Health Insurance Service (NHISS), which includes individuals aged ≥40 years, in cohort 1, cancer-free individuals screened in 2010 were followed until 2017, with HDL-C categorized into eight 10 mg/dL intervals. In cohort 2, individuals screened in 2009 and 2013 were followed until 2017, with HDL-C change classified as persistently normal, normal-to-low, low-to-normal, or persistently low. Among 4.518 million (cohort 1), 33512 patients developed lung cancer. Both low HDL-C (<40 mg/dL) (adjusted hazard ratio [aHR] 1.23; 95% confidence interval [CI] 1.12-1.35) and the highest HDL-C (≥80 mg/dL) (aHR 1.11; 95% CI 1.01-1.21) was associated with an increased lung cancer risk, particularly in men and ever-smokers. Among 2.8 million (cohort 2), 12055 patients developed lung cancer. HDL-C changes from normal to low levels increased lung cancer risk (aHR 1.14; 95% CI 1.08-1.21). Normal-to-low HDL-C change increased the lung cancer risk in men (aHR 1.14; 95% CI 1.05-1.23). The persistently low (aHR 1.24; 95% CI 1.13-1.36), low-to-normal (aHR 1.17; 95% CI 1.07-1.27), and normal-to-low groups (aHR 1.22; 95% CI 1.13-1.32) had a higher lung cancer risk compared with persistently normal HDL-C group among ever-smokers. Our study showed that low and extremely high HDL-C levels increased lung cancer risk, particularly in men and ever-smokers and HDL-C changes from normal to low levels increase lung cancer risk, with discrepancies in sex and smoking status.