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

• Type of Material: Article
• Authors: Sophia S Wang, Beckman Research Institute of City of Hope; Claire M Vajdic, The University of New South Wales; Martha S Linet, National Cancer Institute, National Institutes of Health, Rockville; Susan L Slager, Mayo Clinic, Rochester; Jenna Voutsinas, Beckman Research Institute of City of Hope; Alexandra Nieters, University Medical Center Freiburg; Delphine Casabonne, Institut Català d’ Oncologia/IDIBELL; James R Cerhan, Mayo Clinic, Rochester; Wendy Cozen, University of California Irvine; Graciella Alarcon, University of Alabama Birmingham; Otoniel Martinez-Maza, University of California Los Angeles; Elizabeth E Brown, University of Alabama Birmingham; Paige M Bracci, University of California San Francisco; Jennifer Turner, Douglass Hanly Moir Pathology; Henrik Hjalgrim, Statens Serum Institut; Parveen Bhatti, British Columbia Cancer Research Center; Yawei Zhang, Chinese Acad Med Sci & Peking Union Med Coll; Brenda M Birmann, Brigham and Women's Hospital and Harvard Medical School; Christopher Flowers, Emory University; Ora Palliel, The Hebrew University-Hadassah Braun; Elizabeth A Holly, University of California San Francisco; Eleanor Kane, University of York; Dennis D Weisenburger, City of Hope, Duarte; Marc Maynadié, Burgundy University and University Hospital; Pierluigi Cocco, University of Cagliari; Lenka Foretova, Masaryk Memorial Cancer Institute; Elizabeth C Breen, University of California Los Angeles; Qing Lan, National Cancer Institute, National Institutes of Health, Rockville; Angela Brooks-Wilson, Simon Fraser University; Anneclaire J De Roos, Drexel University; Martyn T Smith, University of California Berkeley; Eve Roman, University of York; Paolo Boffetta, Stony Brook University; Anne Kricker, University of Sydney; Tongzhang Zheng, Brown University; Christine Skibola, Emory University; Jacqueline Clavel, Université de Paris; Alain Monnereau, Université de Paris; Stephen J Chanock, National Cancer Institute, National Institutes of Health, Rockville; Nathaniel Rothman, National Cancer Institute, National Institutes of Health, Rockville; Yolanda Benavente, Institut Català d’ Oncologia/IDIBELL; Patricia Hartge, National Cancer Institute, National Institutes of Health, Rockville; Karin E Smedby, Karolinska University Hospital
• Language: English
• Date: 2022-05-01
• Publisher: AMER ASSOC CANCER RESEARCH
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2022 The Authors; Published by the American Association for Cancer Research
• Final Published Version (URL): http://dx.doi.org/10.1158/1055-9965.EPI-21-0875
• Title of Journal or Parent Work: CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
• Volume: 31
• Issue: 5
• Start Page: 1103
• End Page: 1110
• Grant/Funding Information: EpiLymph: European Commission (grant references QLK4-CT-2000-00422 and FOOD-CT-2006-023103); this work was partially supported by the Institut de Salud Carlos III-ISCIII (Spanish Government) cofunded by FEDER funds/European Regional Development Fund (ERDF) – a way to build Europe (CIBERESP CB06/02/0073, PI17/01280, PI20/00288), AGENCIA DE GESTIO D'AJUTS UNIVERSITARIS I DE RECERCA (2017SGR1085), European Commission (grant references 051210) and had no role in the data collection, analysis, or interpretation of the results; the NIH (contract NO1-CO-12400); the Compagnia di San Paolo—Programma Oncologia; the Federal Office for Radiation Protection grants StSch4261 and StSch4420, the José Carreras Leukemia Foundation grant DJCLS-R12/23, the German Federal Ministry for Education and Research (BMBF-01-EO-1303); the Health Research Board, Ireland and Cancer Research Ireland; Czech Republic supported by MH CZ – DRO (MMCI, 00209805) and MEYS – NPS I – LO1413; Fondation de France and Association de Recherche Contre le Cancer (France: M. Maynadié, A. Monnereau; Germany: A. Nieters; Spain: Y. Benavente, D. Casabonne; Czech Republic: L. Foretova; Italy: P. Boffetta).; Mayo Clinic Case-Control Study: NIH (R01 CA92153; R01 CA200703); NCI (P30 CA015083, to J.R. Cerhan, S.L. Slager).; This work was supported by NIH grants R03 CA179558 [to S. S. Wang, principal investigator (PI), City of Hope, Duarte, CA].; SCALE: Swedish Cancer Society (2009/659), Stockholm County Council (20110209), and the Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Cancer Society grant (02 6661); NIH (5R01 CA69669-02); Plan Denmar. (to K.E. Smedby, H. Hjalgrim).; Yale University Study: NCI (CA62006 and CA165923; to T. Zheng, Y. Zhang); British Columbia Study: National Cancer Institute of Canada, Canadian Cancer Society; the Canadian Institutes of Health Research (CIHR), and the Michael Smith Foundation for Health Research (to P. Bhatti, A. Brooks-Wilson, PI: John Spinelli).; United Kingdom study: Blood Cancer UK (to E. Kane, E. Roman); ENGELA: Association pour la Recherche contre le Cancer (ARC), Institut National du Cancer (INCa), Fondation de France, Fondation contre la Leucémie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES; to A. Monnereau, M. Maynadié, J. Clavel).; New South Wales study: The Australian National Health and Medical Research Council (ID990920), the Cancer Council NSW, and the University of Sydney Foundation Program (to C.M. Vadjic, J. Turner, A. Kricker).; UCSF1 and UCSF2: The UCSF studies were supported by the NCI, NIH (grant nos. CA45614, CA89745, CA87014, CA1046282, and CA154643). The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the NCI's SEER Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California (to E.A. Holly, P.M. Bracci, C.F Skibola, M.T Smith).; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; NCI-SEER study: Intramural Research Program of the NCI, NIH, and Public Health Service (N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105; to P. Hartge, N. Rothman, S.J. Chanock).; This work was also supported by:
• Keywords: Oncology; NON-HODGKIN-LYMPHOMA; Public, Environmental & Occupational Health; EPIDEMIOLOGIC RESEARCH; Life Sciences & Biomedicine; GENOME-WIDE ASSOCIATION; NEOPLASMS; SUSCEPTIBILITY LOCI; Science & Technology; DISORDERS; CLASSIFICATION; MEDICAL HISTORY
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pathology; Environmental Sciences; Health Sciences, Oncology

Abstract

Background: 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. Methods: 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 ¼ 1,914), follicular lymphoma (n ¼ 1,733), and marginal zone lymphoma (MZL; n ¼ 407), using unconditional logistic regression. Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR ¼ 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR ¼ 1.81; 95% CI, 1.59–2.07; P-trend (Ptrend) < 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 ¼ 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend < 0.0001, P-interaction (Pinteraction) ¼ 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. Conclusions: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. Impact: 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.