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, F Xavier 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

    Research output: Contribution to journalArticlepeer-review

    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 We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph).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
    Pages (from-to)27-38
    Number of pages12
    JournalThe Lancet. Oncology
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - Jan 2006

    Keywords

    • Case-Control Studies
    • Genetic Predisposition to Disease
    • Genotype
    • Humans
    • Inflammation
    • Interleukin-10
    • Lymphoma, Non-Hodgkin
    • Pedigree
    • Polymorphism, Single Nucleotide
    • Risk Factors
    • Tumor Necrosis Factor-alpha
    • Journal Article
    • Research Support, N.I.H., Extramural
    • Research Support, N.I.H., Intramural
    • Research Support, Non-U.S. Gov't

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