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Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. 2015
Sophia S Wang, and
Claire M Vajdic, and
Martha S Linet, and
Susan L Slager, and
Jenna Voutsinas, and
Alexandra Nieters, and
Silvia de Sanjose, and
Wendy Cozen, and
Graciela S Alarcón, and
Otoniel Martinez-Maza, and
Elizabeth E Brown, and
Paige M Bracci, and
Tracy Lightfoot, and
Jennifer Turner, and
Henrik Hjalgrim, and
John J Spinelli, and
Tongzhang Zheng, and
Lindsay M Morton, and
Brenda M Birmann, and
Christopher R Flowers, and
Ora Paltiel, and
Nikolaus Becker, and
Elizabeth A Holly, and
Eleanor Kane, and
Dennis Weisenburger, and
Marc Maynadie, and
Pierluigi Cocco, and
Lenka Foretova, and
Anthony Staines, and
Scott Davis, and
Richard Severson, and
James R Cerhan, and
Elizabeth C Breen, and
Qing Lan, and
Angela Brooks-Wilson, and
Anneclaire J De Roos, and
Martyn T Smith, and
Eve Roman, and
Paolo Boffetta, and
Anne Kricker, and
Yawei Zhang, and
Christine Skibola, and
Stephen J Chanock, and
Nathaniel Rothman, and
Yolanda Benavente, and
Patricia Hartge, and
Karin E Smedby
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).
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