Obesity-specific association of statin use and reduced risk of recurrence of early-stage non-small cell lung cancer

Abstract Introduction Statins, used for their lipid-lowering activity, have anti-inflammatory and anti-cancer properties as well. We examined this potential benefit of statin use in patients with non-small cell lung cancer (NSCLC). Methods All 613 patients with pathologic stage I/II NSCLC who had lobectomy without neoadjuvant therapy at our institution during 2008–15 were included. Association between pre-surgery statin use and overall (OS) and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression. Association of statin use with tumor transcriptome was examined in another 350 lung cancer cases. Results Univariable analyses did not demonstrate a statistically significant association of statin use with either OS or RFS, with hazard ratio (HR) = 1.19 and 0.70 (Wald p=0.28 and 0.09), respectively. In subgroup analyses, significantly improved RFS was seen in statin users, but only in overweight/obese patients (BMI > 25; n=422), with univariable and multivariable HR of 0.49 and 0.46 (p = 0.005 and 0.002), respectively, but not in patients with BMI ≤ 25 (n = 191; univariable p=0.21). Transcriptomes of tumors statin users had high expression of tumoricidal genes such as granzyme A and interferon γ compared to non-users among high- but not low-BMI lung cancer patients. Conclusions Our study suggests that statins may improve the outcome of early-stage NSCLC but only in overweight or obese patients. This benefit may stem from a favorable reprogramming of the anti-tumor immune response that statins perpetrate specifically in the obese.