Associations of Non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci

Sophia S. Wang*, Claire M. Vajdic, Martha S. Linet, Susan L. Slager, Jenna Voutsinas, Alexandra Nieters, Silvia De Sanjose, Wendy Cozen, Graciela S. Alarcón, Otoniel Martinez-Maza, Elizabeth E. Brown, Paige M. Bracci, Tracy Lightfoot, Jennifer Turner, Henrik Hjalgrim, John J. Spinelli, Tongzhang Zheng, Lindsay M. Morton, Brenda M. Birmann, Christopher R. FlowersOra Paltiel, Nikolaus Becker, Elizabeth A. Holly, Eleanor Kane, Dennis Weisenburger, Marc Maynadie, Pierluigi Cocco, Lenka Foretova, Anthony Staines, Scott Davis, Richard Severson, James R. Cerhan, Elizabeth C. Breen, Qing Lan, Angela Brooks-Wilson, Anneclaire J. De Roos, Martyn T. Smith, Eve Roman, Paolo Boffetta, Anne Kricker, Yawei Zhang, Christine Skibola, Stephen J. Chanock, Nathaniel Rothman, Yolanda Benavente, Patricia Hartge, Karin E. Smedby

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    39 Citations (Scopus)

    Abstract

    Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).

    Original languageEnglish
    Pages (from-to)406-421
    Number of pages16
    JournalAmerican Journal of Epidemiology
    Volume181
    Issue number6
    DOIs
    Publication statusPublished - 8 Dec 2015

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