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

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, Henrik Hjalgrim, Parveen Bhatti, Yawei Zhang, Brenda M. Birmann, Christopher R. Flowers, Ora PaltielElizabeth 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1103-1110
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume31
Issue number5
DOIs
StatePublished - 4 May 2022

Bibliographical note

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

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