Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: A report from the InterLymph Consortium

Nathaniel Rothman, Christine F. Skibola, Sophia S. Wang, Gareth Morgan, Qing Lan, Martyn T. Smith, John J. Spinelli, Eleanor Willett, Silvia De Sanjose, Pierluigi Cocco, Sonja I. Berndt, Paul Brennan, Angela Brooks-Wilson, Sholom Wacholder, Nikolaus Becker, Patricia Hartge, Tongzhang Zheng, Eve Roman, Elizabeth A. Holly, Paolo BoffettaBruce Armstrong, Wendy Cozen, Martha Linet, Xavier F. Bosch, Maria Grazia Ennas, Theodore R. Holford, Richard P. Gallagher, Sara Rollinson, Paige M. Bracci, James R Cerhan, Denise Whitby, Patrick S. Moore, Brian Leaderer, Agnes Lai, Charlotte Spink, Scott Davis, Ramon Bosch, Aldo Scarpa, Yawei Zhang, Richard K. Severson, Meredith Yeager, Stephen Chanock, Alexandra Nieters

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Abstract

Background: Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). Methods: We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. Findings: The tumour necrosis factor (TNF) -308G→A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T→A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083). Interpretation: Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalLancet Oncology
Volume7
Issue number1
DOIs
StatePublished - Jan 2006

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ASJC Scopus subject areas

  • Oncology

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Rothman, N., Skibola, C. F., Wang, S. S., Morgan, G., Lan, Q., Smith, M. T., Spinelli, J. J., Willett, E., De Sanjose, S., Cocco, P., Berndt, S. I., Brennan, P., Brooks-Wilson, A., Wacholder, S., Becker, N., Hartge, P., Zheng, T., Roman, E., Holly, E. A., ... Nieters, A. (2006). Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: A report from the InterLymph Consortium. Lancet Oncology, 7(1), 27-38. https://doi.org/10.1016/S1470-2045(05)70434-4