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

  1. Author:
    Rothman, N.
    Skibola, C. F.
    Wang, S. S.
    Morgan, G.
    Lon, 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. Z.
    Roman, E.
    Holly, E. A.
    Boffetta, P.
    Armstrong, B.
    Cozen, W.
    Linet, M.
    Bosch, F. X.
    Ennas, M. G.
    Holford, T. R.
    Gallagher, R. P.
    Rollinson, S.
    Bracci, P. M.
    Cerhan, J. R.
    Whitby, D.
    Moore, P. S.
    Leaderer, B.
    Lai, A.
    Spink, C.
    Davis, S.
    Bosch, R.
    Scarpa, A.
    Zhang, Y. W.
    Severson, R. K.
    Yeager, M.
    Chanock, S.
    Nieters, A.

  2. Author Address

    NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. Univ York, Epidemiol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. Catalan Inst Oncol, Epidemiol & Canc Registry Unit, Barcelona, Spain. Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. Univ Cagliari, Dept Cytomorphol, Cagliari, Italy. Int Agcy Res Canc, Unit Environm Canc, F-69372 Lyon, France. German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Dept Hlth & Human Serv, Frederick, MD 21701 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Dept Hlth & Human Serv, Frederick, MD 21701 USA. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Univ Bristol, Dept Pathol & Microbiol, Sch Med Sci, Bristol, Avon, England. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Hosp Verge Cinta, Dept Pathol, Tortosa, Spain. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Kamanos Canc Inst, Detroit, MI USA Rothman, N, NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS8116, Bethesda, MD 20892 USA
    1. Year: 2006
    2. Date: JAN
  2. Journal: Lancet Oncology
    1. 7
    2. 1
    3. Pages: 27-38
  4. Type of Article: Article
  1. 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 nonHodgkin 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 IL 10 -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

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  2. DOI: 10.1016/S1470-2045(05)70434-4
  3. View record in Web of Science®
  4. WOS: 000234575600022

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