A Mendelian Randomization Study on the Causal Relationship between Blood Lipids and Lung Cancer
Authors: Ding LN , Lei CJ , Lei QW , Ma HC , Xiao ZZ , Zhang X , Mo XM , Zhang HB 
Published: June 2023

Abstract
Objective
This study aims to use Mendelian randomization (MR) research method to investigate the causal relationship between blood lipids and lung cancer in both European and East Asian populations through genome-wide association (GWAS) analysis.
Methods
This study utilized data from multiple sources, including the international lung cancer consortium (ILCCO) database and FinnGen database, the UK Biobank (UKB) for European population lung cancer and blood lipid data, respectively. Biobank Japan (BBJ) and the Asian genetic epidemiology network (AGEN) provided data for the East Asian population. To determine the causal relationship between blood lipids and lung cancer, several detection methods were employed, including IVW, MR_Egger, weighted median, simple mode, and weighted mode. In cases of conflicting results, the IVW method was given priority. Heterogeneity and pleiotropy were detected using IVW and MR_Egger tests, and sensitivity analysis was conducted through leave-one-out analysis.
Results
In the study of European and East Asian populations, it was found that high-density lipoprotein (HDL) (IVW: OR = 1.00, 95%CI = 0.90–1.10, P = 0.945), low-density lipoprotein (LDL) ( IVW: OR = 1.05, 95%CI = 0.92–1.19, P = 0.487), triglyceride (TG) (IVW: OR = 1.05, 95%CI = 0.94–1.17, P = 0.399), Apolipoprotein A (Apo A) (IVW: OR = 1.01, 95%CI = 0.92–1.12, P = 0.772), Apolipoprotein B (Apo B) (IVW: OR = 0.97, 95%CI = 0.87–1.07, P = 0.521) had no causal relationship with lung cancer. We then verified the causal relationship of blood lipids in different pathological types of lung cancer. HDL (IVW: OR = 1.10, 95%CI = 0.81–1.49, P = 0.555), TG (IVW: OR = 1.01, 95%CI = 0.73–1.41, P = 0.937), Apo A (IVW: OR = 1.01, 95%CI = 0.74–1.38, P = 0.964), Apo B (IVW: OR = 1.28, 95%CI = 0.95–1.73, P = 0.106) have not significantly associated with the occurrence of lung adenocarcinoma (LUAD), although LDL (IVW: OR = 1.37, 95%CI = 0.96–1.94, P = 0.081) has a tendency but no statistical significance; HDL (IVW: OR = 0.97, 95%CI = 0.67–1.40, P = 0.867), LDL (IVW: OR = 1.27, 95%CI = 0.81-2.00, P = 0.296), TG (IVW: OR = 1.41, 95%CI = 0.96–2.08, P = 0.084), Apo A (IVW: OR = 0.99, 95%CI = 0.67–1.45, P = 0.951), Apo B (IVW: OR = 1.32, 95%CI = 0.90–1.95, P = 0.159) have not significantly associated with the occurrence of lung squamous cell carcinoma (LUSC); HDL (IVW: OR = 1.58, 95%CI = 0.94–2.65, P = 0.082) has a tendency for the occurrence of small cell lung cancer (SCC), but there is no statistical significance. LDL (IVW: OR = 1.39, 95%CI = 0.75–2.59, P = 0.296), TG (IVW: OR = 1.04, 95%CI = 0.60–1.81, P = 0.895), Apo A (IVW: OR = 1.26, 95%CI = 0.73–2.17, P = 0.401), Apo B (IVW: OR = 1.24, 95%CI = 0.73–2.11, P = 0.423) have no causal relationship with the occurrence of SCC. In the East Asian population, HDL (IVW: OR = 1.00, 95%CI = 0.88–1.15, P = 0.956), LDL (IVW: OR = 0.89, 95%CI = 0.78–1.02, P = 0.093), TG (IVW: OR = 0.91, 95%CI = 0.80–1.04, P = 0.157), CHOL (IVW: OR = 0.93, 95%CI = 0.77–1.13, P = 0.493) had no causal relationship with lung cancer obvious statistical significance.
Conclusions
Our research demonstrated that blood lipids HDL, LDL, TG, Apo A, and Apo B do not significantly correlate with lung cancer in the European population. None of the four items of blood lipid (HDL, LDL, TG, CHOL) were discovered to be connected to the development of lung cancer in the East Asian population. According to the aforementioned findings, there is no link between blood lipid levels and the risk of developing lung cancer in East Asian or European populations.