Wang, Sophia S., Vajdic, Claire M., Linet, Martha S. et al. (40 more authors) (2022) B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS. Cancer Epidemiology Biomarkers & Prevention. pp. 1103-1110. ISSN 1055-9965
Abstract
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.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.We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95\CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95\ 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.Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions.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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Health Sciences (York) |
Depositing User: | Pure (York) |
Date Deposited: | 06 Jul 2022 11:10 |
Last Modified: | 21 Jan 2025 18:03 |
Published Version: | https://doi.org/10.1158/1055-9965.EPI-21-0875 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1158/1055-9965.EPI-21-0875 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188788 |
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Description: B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
Licence: CC-BY-NC-ND 2.5