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Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

About this Publication
Title
Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.
Pubmed ID
32108027 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Epidemiol Biomarkers Prev. 2020 May; Volume 29 (Issue 5): Pages 1074-1078
Authors
Kleinstern G, Camp NJ, Berndt SI, Birmann BM, Nieters A, Bracci PM, McKay JD, Ghesquières H, Lan Q, Hjalgrim H, Benavente Y, Monnereau A, Wang SS, Zhang Y, Purdue MP, Zeleniuch-Jacquotte A, Giles GG, Vermeulen R, Cocco P, Albanes D, ...show more Teras LR, Brooks-Wilson AR, Vajdic CM, Kane E, Caporaso NE, Smedby KE, Salles G, Vijai J, Chanock SJ, Skibola CF, Rothman N, Slager SL, Cerhan JR
Affiliations
  • Mayo Clinic, Rochester, Minnesota.
  • Department of Internal Medicine, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City, Utah.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Institute for Immunodeficiency, Medical Center - University of Freiburg, Freiburg, Germany.
  • Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
  • International Agency for Research on Cancer, Lyon, France.
  • Department of Hematology, Centre Hospitalier Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite, France.
  • Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
  • Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
...show more
  • Registre des Hémopathies Malignes de la Gironde, Institut Bergonié, Epidemiology of Childhood and Adolescent Cancers Group, Inserm, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France.
  • City of Hope Beckman Research Institute, Duarte, California.
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.
  • Department of Population Health and Perlmutter Cancer Center, NYU School of Medicine, New York, New York.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • University Medical Center Utrecht, Utrecht, the Netherlands.
  • Department of Medical Sciences and Public Health, Occupational Health Section, University of Cagliari, Monserrato, Italy.
  • American Cancer Society, Atlanta, Georgia.
  • BC Cancer, Vancouver, and Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
  • Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia.
  • Epidemiology and Cancer Statistics Group, Department of Health Sciences, University of York, Heslington, York, United Kingdom.
  • Karolinska Institutet, Division of Clinical Epidemiology, Department of Medicine Solna, Stockholm, Sweden.
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Emory University, Atlanta, Georgia.
  • Mayo Clinic, Rochester, Minnesota. cerhan.james@mayo.edu.
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 × 10-8) 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).

RESULTS: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 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 = 1.08; 95% CI, 0.99-1.19; P = 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.

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