Lipid trait variants and the risk of non-hodgkin lymphoma subtypes: a mendelian randomization study

Geffen Kleinstern, Nicola J. Camp, Sonja I. Berndt, Brenda M. Birmann, Alexandra Nieters, Paige M. Bracci, James D. McKay, Herve Ghesquieres, Qing Lan, Henrik Hjalgrim, Yolanda Benavente, Alain Monnereau, Sophia S. Wang, Yawei Zhang, Mark P. Purdue, Anne Zeleniuch-Jacquotte, Graham G. Giles, Roel Vermeulen, Pierluigi Cocco, Demetrius AlbanesLauren R. Teras, Angela R. Brooks-Wilson, Claire M. Vajdic, Eleanor Kane, Neil E. Caporaso, Karin E. Smedby, Gilles Salles, Joseph Vijai, Stephen J. Chanock, Christine F. Skibola, Nathaniel Rothman, Susan L. Slager, James R. Cerhan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Lipid 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 lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P < 5 108) with high-density lipoprotein (HDL, n ¼ 164), low-density lipoprotein (LDL, n ¼ 137), total cholesterol (TC, n ¼ 161), and triglycerides (TG, n ¼ 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). Results: HDL was positively associated with DLBCL (OR ¼ 1.14; 95% CI, 1.00–1.30) and MZL (OR ¼ 1.09; 95% CI, 1.01–1.18), while TG was inversely associated with MZL risk (OR ¼ 0.90; 95% CI, 0.83–0.99), all at nominal significance (P < 0.05). A positive trend was observed for HDL with FL risk (OR ¼ 1.08; 95% CI, 0.99–1.19; P ¼ 0.087). No associations were noteworthy after adjusting for multiple testing. Conclusions: We 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. Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.

Original languageEnglish (US)
JournalCancer Epidemiology Biomarkers and Prevention
Volume29
Issue number5
DOIs
StatePublished - May 2020

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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