HDL Cholesterol Levels and Pancreatic Cancer Risk: Protective Effects Revealed.

Abstract

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

Methods: Univariable MR analyses were used to determine the causal connection between lipo-protein 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.

Results: In univariable MR, IVW methods 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 smok-ing, alcohol consumption, and body mass index (BMI).

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