Abstract
BACKGROUND: Current evidence on relationships between serum lipid biomarkers and the risk of gastrointestinal cancers remains controversial, with no consensus reached. METHODS: We conducted a prospective cohort study within the Kailuan Cohort wherein 88,225 individuals with baseline information on triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was followed from 2006 to 2021 for the incidence of esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Increased EC risk was associated with high HDL-C levels (HR(Q4vs.Q1) = 2.50, 95% CI: 1.57-3.98), while a U-shaped relationship between HDL-C and EC risk was revealed in the RCS analysis (p(overall) ≤ 0.0001, p(nonlinear) = 0.02). No robust association was identified between lipid biomarkers and GC risk. In multivariable analysis, increased CRC risk was positively associated with high TC levels (HR(Q4vs.Q1) = 1.42, 95% CI: 1.11-1.83, p(trend) = 0.03), dose-responsely negatively associated with LDL-C levels over quartiles (HR(Q2vs.Q1) = 0.83, 95% CI: 0.66-1.02; HR(Q3vs.Q1) = 0.86, 95% CI: 0.69-1.07; HR(Q4vs.Q1) = 0.68, 95% CI: 0.53-0.86, p(trend) = 0.02), and showed a diminished negative association with HDL-C levels over quartiles (HR(Q2vs.Q1) = 0.75, 95% CI: 0.60-0.94; HR(Q3vs.Q1) = 0.76, 95% CI: 0.61-0.95; HR(Q4vs.Q1) = 0.91, 95% CI 0.74-1.13, p(trend) = 0.02). The subsequent RCS analysis revealed a linear negative relationship of LDL-C (p(overall) = 0.004, p(nonlinear) = 0.67) and a U-shaped relationship of HDL-C (p(overall) = 0.05, p(nonlinear) = 0.02) with CRC risk. Competitive risk analysis and sensitivity analysis confirmed the stability of our results. CONCLUSION: We observed a U-shaped relationship regarding HDL-C levels with EC and CRC risk, and a linear inverse relationship between LDL-C levels and CRC risk. Relevant serum lipid levels should be properly managed in high-risk individuals of certain gastrointestinal cancers.