B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Sophia S. Wang
(1)
,
Claire M. Vajdic
(2)
,
Martha S. Linet
(3)
,
Susan L. Slager
(4)
,
Jenna Voutsinas
(1)
,
Alexandra Nieters
(5)
,
Delphine Casabonne
(6, 7)
,
James R. Cerhan
(4)
,
Wendy Cozen
(8)
,
Graciela Alarcon
(9)
,
Otoniel Martinez-Maza
(10)
,
Elizabeth E. Brown
(9)
,
Paige M. Bracci
(11)
,
Jennifer Turner
(12)
,
Henrik Hjalgrim
(13)
,
Parveen Bhatti
(14)
,
Yawei Zhang
(15)
,
Brenda M. Birmann
(16)
,
Christopher R. Flowers
(17)
,
Ora Paltiel
(18)
,
Elizabeth A. Holly
(11)
,
Eleanor Kane
(19)
,
Dennis D. Weisenburger
(20)
,
Marc Maynadie
(21, 22)
,
Pierluigi Cocco
(23)
,
Lenka Foretova
(24)
,
Elizabeth Crabb Breen
(10)
,
Qing Lan
(3)
,
Angela Brooks-Wilson
(25)
,
Anneclaire J. de Roos
(26)
,
Martyn T. Smith
(27)
,
Eve Roman
(19)
,
Paolo Boffetta
(28, 29)
,
Anne Kricker
(30)
,
Tongzhang Zheng
(31)
,
Christine F. Skibola
(17)
,
Jacqueline Clavel
(32)
,
Alain Monnereau
(33, 34, 32, 35)
,
Stephen J. Chanock
(3)
,
Nathaniel Rothman
(3)
,
Yolanda Benavente
(6, 7)
,
Patricia Hartge
(3)
,
Karin E. Smedby
(36)
1
Beckman Research Institute of the City of Hope
2 UNSW - University of New South Wales [Sydney]
3 NCI-NIH - National Cancer Institute [Bethesda]
4 Mayo Clinic [Rochester]
5 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
6 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge = Bellvitge Biomedical Research Institute
7 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
8 UC Irvine - University of California [Irvine]
9 UAB - University of Alabama at Birmingham [ Birmingham]
10 UCLA - University of California [Los Angeles]
11 UC San Francisco - University of California [San Francisco]
12 Macquarie University [Sydney]
13 Statens Serum Institut [Copenhagen]
14 British Columbia Cancer Research Centre [British Columbia, Canada]
15 China Academy of Chinese Medical Sciences
16 HMS - Harvard Medical School [Boston]
17 Emory University [Atlanta, GA]
18 Hadassah Hebrew University Medical Center [Jerusalem]
19 University of York [York, UK]
20 City of Hope Comprehensive Cancer Center [Duarte]
21 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
22 CHU Dijon
23 University of Cagliari
24 MMCI - Masaryk Memorial Cancer Institute
25 SFU.ca - Simon Fraser University = Université Simon Fraser
26 Drexel University
27 UC Berkeley - University of California [Berkeley]
28 SBU - Stony Brook University [SUNY]
29 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
30 The University of Sydney
31 Brown University
32 CRESS - Centre for Research in Earth and Space Science [Toronto]
33 BPH - Bordeaux population health
34 EPICENE - Cancer environnement
35 Institut Bergonié [Bordeaux]
36 Karolinska Institutet [Stockholm]
2 UNSW - University of New South Wales [Sydney]
3 NCI-NIH - National Cancer Institute [Bethesda]
4 Mayo Clinic [Rochester]
5 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
6 IDIBELL - Institut d'Investigació Biomèdica de Bellvitge = Bellvitge Biomedical Research Institute
7 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
8 UC Irvine - University of California [Irvine]
9 UAB - University of Alabama at Birmingham [ Birmingham]
10 UCLA - University of California [Los Angeles]
11 UC San Francisco - University of California [San Francisco]
12 Macquarie University [Sydney]
13 Statens Serum Institut [Copenhagen]
14 British Columbia Cancer Research Centre [British Columbia, Canada]
15 China Academy of Chinese Medical Sciences
16 HMS - Harvard Medical School [Boston]
17 Emory University [Atlanta, GA]
18 Hadassah Hebrew University Medical Center [Jerusalem]
19 University of York [York, UK]
20 City of Hope Comprehensive Cancer Center [Duarte]
21 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
22 CHU Dijon
23 University of Cagliari
24 MMCI - Masaryk Memorial Cancer Institute
25 SFU.ca - Simon Fraser University = Université Simon Fraser
26 Drexel University
27 UC Berkeley - University of California [Berkeley]
28 SBU - Stony Brook University [SUNY]
29 UNIBO - Alma Mater Studiorum Università di Bologna = University of Bologna
30 The University of Sydney
31 Brown University
32 CRESS - Centre for Research in Earth and Space Science [Toronto]
33 BPH - Bordeaux population health
34 EPICENE - Cancer environnement
35 Institut Bergonié [Bordeaux]
36 Karolinska Institutet [Stockholm]
Résumé
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 = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. RESULTS: 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) < 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 < 0.0001, P-interaction (Pinteraction) = 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.
Domaines
Santé publique et épidémiologieOrigine | Fichiers éditeurs autorisés sur une archive ouverte |
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