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Title: B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Author: Wang, Sophia S.
Vajdic, Claire M.
Linet, Martha S.
Slager, Susan L.
Voutsinas, Jenna
Nieters, Alexandra
Casabonne, Delphine
Cerhan, James R.
Cozen, Wendy
Alarcón, Graciela
Martínez Maza, Otoniel
Brown, Elizabeth E.
Bracci, Paige M.
Turner, Jennifer
Hjalgrim, Henrik
Bhatti, Parveen
Zhang, Yawei
Birmann, Brenda M.
Flowers, Christopher R.
Paltiel, Ora
Holly, Elizabeth A.
Kane, Eleanor
Weisenburger, Dennis D.
Maynadié, Marc
Cocco, Pierluigi
Foretova, Lenka
Breen, Elizabeth Crabb
Lan, Qing
Brooks-Wilson, Angela
Roos, Anneclaire J. de
Smith, Martyn T.
Roman, Eve
Boffetta, Paolo
Kricker, Anne
Zheng, Tongzhang
Skibola, Christine F.
Clavel, Jacqueline
Monnereau, Alain
Chanock, Stephen J.
Rothman, Nathaniel
Benavente, Yolanda
Hartge, Patricia
Smedby, Karin E.
Keywords: Malalties autoimmunitàries
Autoimmune diseases
Issue Date: 24-Feb-2022
Publisher: American Association for Cancer Research (AACR)
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 = 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 (P-trend) < 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 anda T3 PRS [OR = 6.46 vs. no autoimmune condition anda T1 PRS, P-trend < 0.0001, P-interaction (P-interaction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant P-interaction. 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.
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It is part of: Cancer Epidemiology, Biomarkers & Prevention, 2022, vol. 31, num. 5, p. 1103-1110
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ISSN: 1538-7755
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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