B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS

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  • Sophia S. Wang
    1Division of Health Analytics, Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Monrovia, California.
  • Claire M. Vajdic
    2Centre for Big Data Research in Health, The University of New South Wales, Sydney, New South Wales, Australia.
  • Martha S. Linet
    3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
  • Susan L. Slager
    4Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Jenna Voutsinas
    1Division of Health Analytics, Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Monrovia, California.
  • Alexandra Nieters
    5The Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
  • Delphine Casabonne
    6Unit of Infections and Cancer, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program – Epibell, IDIBELL, Institut Català d’ Oncologia/IDIBELL, Barcelona, Spain.
  • James R. Cerhan
    4Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Wendy Cozen
    8Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, California.
  • Graciela Alarcón
    9Division of Clinical Immunology and Rheumatology, Department of Medicine, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
  • Otoniel Martínez-Maza
    10Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
  • Elizabeth E. Brown
    13Department of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama.
  • Paige M. Bracci
    15Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
  • Jennifer Turner
    16Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia.
  • Henrik Hjalgrim
    18Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Parveen Bhatti
    19British Columbia Cancer Research Center, Vancouver, British Columbia, Canada.
  • Yawei Zhang
    20Department of Cancer Prevention and Control at the National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Brenda M. Birmann
    21Channing Division of Network Medicine, Department of Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Christopher R. Flowers
    22Winship Cancer Institute, Emory University, Atlanta, Georgia.
  • Ora Paltiel
    23Department of Hematology, The Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Hadassah University Medical Center, Jerusalem, Israel.
  • Elizabeth A. Holly
    15Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
  • Eleanor Kane
    24Department of Health Sciences, University of York, York, United Kingdom.
  • Dennis D. Weisenburger
    25Department of Pathology, City of Hope, Duarte, California.
  • Marc Maynadié
    26Registry of Hematological Malignancies of Cote d'Or, INSERM U1231, Burgundy University and University Hospital, Dijon, France (Maynadie).
  • Pierluigi Cocco
    27Occupational Health Section, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
  • Lenka Foretova
    28Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
  • Elizabeth Crabb Breen
    29Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
  • Qing Lan
    3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
  • Angela Brooks-Wilson
    30Department of Biomedical Physiology and Kinesiology, Faculty of Science, Simon Fraser University, Vancouver, British Columbia, Canada.
  • Anneclaire J. De Roos
    31Department of Environmental and Occupational Health, Dornsife School of Public Health, Drexel University, Philadelphia, Pennsylvania.
  • Martyn T. Smith
    32Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, California.
  • Eve Roman
    24Department of Health Sciences, University of York, York, United Kingdom.
  • Paolo Boffetta
    33Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York.
  • Anne Kricker
    35Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Tongzhang Zheng
    36Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island.
  • Christine F. Skibola
    22Winship Cancer Institute, Emory University, Atlanta, Georgia.
  • Jacqueline Clavel
    37Centre of Research in Epidemiology and Statistics (CRESS), UMR1153, INSERM, Université de Paris, Paris, France.
  • Alain Monnereau
    37Centre of Research in Epidemiology and Statistics (CRESS), UMR1153, INSERM, Université de Paris, Paris, France.
  • Stephen J. Chanock
    3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
  • Nathaniel Rothman
    3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
  • Yolanda Benavente
    6Unit of Infections and Cancer, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program – Epibell, IDIBELL, Institut Català d’ Oncologia/IDIBELL, Barcelona, Spain.
  • Patricia Hartge
    3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
  • Karin E. Smedby
    39Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background:</jats:title> <jats:p>A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non–Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell–mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59–2.07; P-trend (Ptrend) &lt; 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell–mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend &lt; 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions.</jats:p> </jats:sec> <jats:sec> <jats:title>Impact:</jats:title> <jats:p>Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.</jats:p> </jats:sec>

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