Causal Relationship Between Plasma Lipidome and Six Types of Cancer: A Mendelian Randomization Study

Abstract

Abstract Background: The plasma lipidome is intricately associated with cancer. However, the causal relationship between them remains uncertain. Therefore, this study employs Mendelian randomization (MR) based on genetic principles to investigate the potential causal relationship between plasma lipidome and six common types of cancer. Methods: MR analysis utilizes publicly available genetic data, employing a genome-wide association study (GWAS) of 179 lipid species as exposure and GWAS datasets of six different cancers as outcomes. The inverse variance weighted (IVW) method serves as the primary approach, with MR-Egger regression and weighted median (WM) method employed as supplementary methods for analysis. Additionally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis are conducted to assess the reliability and stability of causal relationships. The Steiger test is also utilized to determine the directionality of causal relationships. Results: The IVW analysis reveals that phosphatidylethanolamine (16:0_20:4) levels and others are implicated as risk factors for hepatic cancer, while sphingomyelin (d40:1) levels and others are identified as protective factors against hepatic cancer. Sterol ester (27:1/20:4) levels and others are associated with increased risk of lung cancer, whereas sterol ester (27:1/18:2) levels and others are associated with decreased risk of lung cancer. Sterol ester (27:1/20:3) levels and others are identified as risk factors for colorectal cancer, whereas phosphatidylcholine (18:2_0:0) levels and others are protective against colorectal cancer. Phosphatidylcholine (16:0_20:4) levels and others are linked to increased risk of esophageal cancer, while phosphatidylcholine (16:0_18:3) levels and others are associated with protection against esophageal cancer. Phosphatidylinositol (18:0_20:4) levels and others are identified as risk factors for thyroid cancer, whereas phosphatidylinositol (16:0_18:2) levels and others are protective against thyroid cancer. Diacylglycerol (18:1_18:2) levels and others are identified as protective factors against breast cancer. Conclusions: There exists a clear causal relationship between plasma lipidome and six types of cancer. Additionally, it has been observed that the same single-nucleotide polymorphisms (SNPs) serve as instrumental variables (IVs), influencing cancer through the plasma lipidome. This provides further avenues and methodologies for early screening and effective treatment of cancer.