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

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  • Sophia S. Wang
  • Claire M. Vajdic
  • Martha S. Linet
  • Susan L. Slager
  • Jenna Voutsinas
  • Alexandra Nieters
  • Delphine Casabonne
  • James R. Cerhan
  • Wendy Cozen
  • Graciela Alarcón
  • Otoniel Martínez-Maza
  • Elizabeth E. Brown
  • Paige M. Bracci
  • Jennifer Turner
  • Parveen Bhatti
  • Yawei Zhang
  • Brenda M. Birmann
  • Christopher R. Flowers
  • Ora Paltiel
  • Elizabeth A. Holly
  • Eleanor Kane
  • Dennis D. Weisenburger
  • Marc Maynadié
  • Pierluigi Cocco
  • Lenka Foretova
  • Elizabeth Crabb Breen
  • Qing Lan
  • Angela Brooks-Wilson
  • Anneclaire J. De Roos
  • Martyn T. Smith
  • Eve Roman
  • Paolo Boffetta
  • Anne Kricker
  • Tongzhang Zheng
  • Christine F. Skibola
  • Jacqueline Clavel
  • Alain Monnereau
  • Stephen J. Chanock
  • Nathaniel Rothman
  • Yolanda Benavente
  • Patricia Hartge
  • Karin E. Smedby

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.

OriginalsprogEngelsk
TidsskriftCancer Epidemiology Biomarkers and Prevention
Vol/bind31
Udgave nummer5
Sider (fra-til)1103-1110
Antal sider8
ISSN1055-9965
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
This work was supported by NIH grants R03 CA179558 [to S. S. Wang, principal investigator (PI), City of Hope, Duarte, CA]. This work was also supported by: 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). 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). 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). 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). 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). 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). 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). United Kingdom study: Blood Cancer UK (to E. Kane, E. Roman) Yale University Study: NCI (CA62006 and CA165923; to T. Zheng, Y. Zhang)

Funding Information:
C.M. Vajdic reports grants from Cancer Council NSW during the conduct of the study. A. Nieters reports grants from Jose Carreras Foundation and European Union during the conduct of the study. J.R. Cerhan reports grants from NIH during the conduct of the study as well as grants from Genentech, NanoString, Bristol-Myers Squibb and other support from Bristol-Myers Squibb and Regeneron Genetics Center outside the submitted work. O. Martinez-Maza reports grants from NIH during the conduct of the study. P.M. Bracci reports grants from NIH during the conduct of the study. H. Hjalgrim reports grants from NIH, Danish Cancer Society, and Danish National Research Council during the conduct of the study. C.R. Flowers reports personal fees from AbbVie, Bayer HealthCare, BeiGene, Celgene, Denovo Biopharma, Epizyme/Incyte, Genentech/Roche, Genmab, Gilead, Karyopharm, MEI Pharmaceuticals, MorphoSys AG Pharmacyclics/Janssen, SeaGen, and Spectrum and grants from 4D, AbbVie, Acerta, Adaptimmune, Allogene, Amgen, Bayer HealthCare, Celgene, Cellectis, EMD, Gilead, Genentech/Roche, Guardant, Iovance, Janssen Pharmaceutical, Kite, Morphosys, Nektar, Novartis, Pfizer, Pharmacyclics, Sanofi-Aventis, Takeda, TG Therapeutics, Xencor, Ziopharm, Burroughs Wellcome Fund, Eastern Cooperative Oncology Group, NCI, V Foundation, and Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research outside the submitted work. E. Kane reports grants from Blood Cancer UK during the conduct of the study. M. Maynadiéreports expertise for Janssen. E.C. Breen reports grants from NIH during the conduct of the study. M.T. Smith reports personal fees from law firms outside the submitted work. E. Roman reports grants from Blood Cancer UK during the conduct of the study. No disclosures were reported by the other authors.

Funding Information:
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).

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 UNIVERSI-TARIS 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 JoséCarreras 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).

Funding Information:
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). United Kingdom study: Blood Cancer UK (to E. Kane, E. Roman) Yale University Study: NCI (CA62006 and CA165923; to T. Zheng, Y. Zhang) 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.

Funding Information:
This work was supported by NIH grants R03 CA179558 [to S. S. Wang, principal investigator (PI), City of Hope, Duarte, CA]. This work was also supported by: 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).

Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research

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