HDL Cholesterol Levels and Pancreatic Cancer Risk: Protective Effects Revealed

The causal relationship between lipoprotein traits and the risk of pancreatic cancer (PC) remains unclear. In this study, we employed a two-sample Mendelian randomization (MR) approach to explore the untangled relationship between lipoprotein traits and PC.

Univariable MR analyses were used to determine the causal connection between lipoprotein traits and PC. Instrumental variables corresponding to lipoprotein traits were taken from the Global Lipids Genetics Consortium (GLGC) (n = 188,578). The outcome dataset was created from PC summary-level data (n case = 1896, n control = 1939) from a genome-wide association study of European ancestry. Causal effects were evaluated using the inverse variance weighted (IVW) method. For sensitivity analysis, both the weighted median (WM) and MR-Egger methods, among others, were utilized. We also conducted multivariable MR analyses to examine potential confounders.

In univariable MR, IVWmethods supported evidence that HDL cholesterol (OR = 0.463, 95% CI: 0.313-0.685; p = 1.10×10-4) was linked with a decreased risk of PC. These findings were consistent across other MR methods, including MR-Egger (OR = 0.340, 95% CI: 0.182- 0.638; p = 1.30×10-3) and WM (OR = 0.367, 95% CI: 0.195-0.692; p = 1.90×10-3). Our results displayed no significant heterogeneity or horizontal pleiotropy. Furthermore, these associations persisted in the multivariable MR analysis after adjusting for confounding factors such as smoking, alcohol consumption, and body mass index (BMI).

Our comprehensive MR analyses consistently demonstrate a protective association between higher HDL cholesterol levels and decreased PC risk, even after adjustments for key lifestyle factors and BMI.