Obesity-Specific Association of Statin Use and Reduced Risk of Recurrence of Early Stage NSCLC

Abstract

Introduction Statins, used for their lipid-lowering activity, have anti-inflammatory and anticancer properties as well. We evaluated this potential benefit of statin use in patients with NSCLC. Methods All 613 patients with pathologic stage 1 or 2 NSCLC who had lobectomy without neoadjuvant therapy at our institution during 2008 to 2015 were included. Association between presurgery statin use and overall survival and recurrence-free survival (RFS) was analyzed using Cox proportional hazards regression. Association of statin use with tumor transcriptome was evaluated in another 350 lung cancer cases. Results Univariable analyses did not reveal a statistically significant association of statin use with either overall survival or RFS, with hazard ratio equals to 1.19 and 0.70 (Wald p = 0.28 and 0.09), respectively. In subgroup analyses, significantly improved RFS was found in statin users, but only in overweight/obese patients (body mass index [BMI] > 25; n = 422), with univariable and multivariable hazard ratio of 0.49 and 0.46 ( p = 0.005 and 0.002), respectively, but not in patients with BMI less than or equal to 25 (n = 191; univariable p = 0.21). Transcriptomes of tumor statin users had high expression of tumoricidal genes such as granzyme A and interferon-γ compared with those of nonusers among high- but not low-BMI patients with lung cancer. 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 antitumor immune response that statins perpetrate specifically in the obese.

The anticancer effect of statins in obese esophageal cancer patients undergoing esophagectomy

“…Obesity as a confounder was reported in a study from our institution which demonstrated a survival benefit in use of the antidiabetic drug metformin in NSCLC, but only in patients who were overweight or obese 25 . Recently published data from our institution has also demonstrated a survival benefit with statins in NSCLC, but only in patients with BMI ≥ 30 24 …”

“…25 Recently published data from our institution has also demonstrated a survival benefit with statins in NSCLC, but only in patients with BMI ≥ 30. 24 There are multiple proposed mechanisms for the antitumor effects of statins. Antiproliferative effects mediated by blocking the transition of G1-S in the cell cycle, apoptosis induction via products of the mevalonate pathway, inhibition of angiogenesis, and inhibition of cell signaling pathways associated with invasion and metastases have been demonstrated.…”

“…Obesity creates a chronic inflammatory state which leads to increased rates of carcinogenesis and tumor progression 21,22 . One of the proposed anticancer mechanisms of statins is their anti‐inflammatory effect, 23 and a previous study from our institution has demonstrated a survival benefit with statins in non‐small cell lung cancer (NSCLC), but only in patients with BMI ≥ 30 24 …”

“…21,22 One of the proposed anticancer mechanisms of statins is their anti-inflammatory effect, 23 and a previous study from our institution has demonstrated a survival benefit with statins in non-small cell lung cancer (NSCLC), but only in patients with BMI ≥ 30. 24 Therefore, we hypothesize that statin usage has an association on esophageal cancer recurrence and survival after esophagectomy, and that the effect of this association may be stronger in patients with high BMI. We analyzed our institutional data on esophagectomies to determine whether this effect was present.…”

Exploring the Impact of the Obesity Paradox on Lung Cancer and Other Malignancies

“…In patients who are overweight or obese, statin use was associated with improved recurrence-free survival [161]. These higher-BMI patients who used statin were found to have higher expression of granzyme A and interferon-γ, which are tumoricidal [161].…”