Cancer Epidemiol Biomarkers Prev

Abstract

BackgroundLipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular (FL) and marginal zone (MZL) lymphoma using Mendelian randomization (MR) analysis.MethodsGWAS data from the InterLymph Consortium were available for 2661 DLBCLs, 2179 CLLs, 2142 FLs, 824 MZLs, and 6221 controls. SNPs associated (P<5 710 128) with high-density lipoprotein (HDL, N=164), low-density lipoprotein (LDL, N=137), total cholesterol (TC, N=161), and triglycerides (TG, N=123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8% and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation, and 95% confidence intervals (CI).ResultsHDL was positively associated with DLBCL (OR=1.14, CI:1.00\u20131.30) and MZL (OR=1.09, CI:1.01\u20131.18), while TG was inversely associated with MZL risk (OR=0.90, CI:0.83\u20130.99) all at nominal significance (P<0.05). A positive trend was observed for HDL with FL risk (OR=1.08, CI:0.99\u20131.19; P=0.087). No associations were noteworthy after adjusting for multiple testing.ConclusionsWe did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.ImpactOur results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.R25 CA092049/CA/NCI NIH HHS/United StatesP30 CA016087/CA/NCI NIH HHS/United StatesUL1 TR000135/TR/NCATS NIH HHS/United StatesR01 CA134958/CA/NCI NIH HHS/United StatesCIHR/CanadaUM1 CA167552/CA/NCI NIH HHS/United StatesU01 HG007033/HG/NHGRI NIH HHS/United StatesHHSN261201000035C/CA/NCI NIH HHS/United StatesHHSN261201000034C/CA/NCI NIH HHS/United StatesHHSN261201000140C/CA/NCI NIH HHS/United StatesR01 CA098122/CA/NCI NIH HHS/United StatesR01 CA149445/CA/NCI NIH HHS/United StatesU58 DP000807/DP/NCCDPHP CDC HHS/United StatesUM1 CA182934/CA/NCI NIH HHS/United StatesUM1 CA186107/CA/NCI NIH HHS/United StatesR01 CA200703/CA/NCI NIH HHS/United StatesR01 CA129539/CA/NCI NIH HHS/United States2020-11-01T00:00:00Z32108027PMC71964908751vault:3543