This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, S. S. Articles by Rothman, N. Search for Related Content PubMed PubMed Citation Articles by Wang, S. S. Articles by Rothman, N.

Common Genetic Variants in Proinflammatory and Other Immunoregulatory Genes and Risk for Non-Hodgkin Lymphoma

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland; ² Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota; ³ University of Iowa, Iowa City, Iowa; ⁴ Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington; ⁵ University of Southern California, Los Angeles, California; ⁶ Karmanos Cancer Institute and Department of Family Medicine, Wayne State University, Detroit, Michigan; and ⁷ Core Genotyping Facility, Advanced Technology Corp., National Cancer Institute, Gaithersburg, Maryland

Requests for reprints: Sophia S. Wang, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS MSC 7234, Bethesda, MD 20892-7234. Phone: 301-402-5374; Fax: 301-402-0916; E-mail: wangso{at}mail.nih.gov.

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor- and lymphotoxin- (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P_trend = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets. (Cancer Res 2006; 66(19): 9771-80)

This article has been cited by other articles:

				J. R. Cerhan, S. M. Ansell, Z. S. Fredericksen, N. E. Kay, M. Liebow, T. G. Call, A. Dogan, J. M. Cunningham, A. H. Wang, W. Liu-Mares, et al. Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma Blood, December 15, 2007; 110(13): 4455 - 4463. [Abstract] [Full Text] [PDF]

				L.-L. Hu, X.-X. Wang, X. Chen, J. Chang, C. Li, Y. Zhang, J. Yang, W. Jiang, and S.-M. Zhuang BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma Carcinogenesis, August 1, 2007; 28(8): 1740 - 1744. [Abstract] [Full Text] [PDF]

				C. F. Skibola, J. D. Curry, and A. Nieters Genetic susceptibility to lymphoma Haematologica, July 1, 2007; 92(7): 960 - 969. [Abstract] [Full Text] [PDF]

				J. R. Cerhan, S. Wang, M. J. Maurer, S. M. Ansell, S. M. Geyer, W. Cozen, L. M. Morton, S. Davis, R. K. Severson, N. Rothman, et al. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival Blood, June 15, 2007; 109(12): 5439 - 5446. [Abstract] [Full Text] [PDF]

				S. S. Wang, W. Cozen, J. R. Cerhan, J. S. Colt, L. M. Morton, E. A. Engels, S. Davis, R. K. Severson, N. Rothman, S. J. Chanock, et al. Immune Mechanisms in Non-Hodgkin Lymphoma: Joint Effects of the TNF G308A and IL10 T3575A Polymorphisms with Non-Hodgkin Lymphoma Risk Factors Cancer Res., May 15, 2007; 67(10): 5042 - 5054. [Abstract] [Full Text] [PDF]

				M. P. Purdue, Q. Lan, A. Kricker, A. E. Grulich, C. M. Vajdic, J. Turner, D. Whitby, S. Chanock, N. Rothman, and B. K. Armstrong Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin Lymphoma Study Carcinogenesis, March 1, 2007; 28(3): 704 - 712. [Abstract] [Full Text] [PDF]

				L. R. Goldin and S. L. Slager Familial CLL: Genes and Environment Hematology, January 1, 2007; 2007(1): 339 - 345. [Abstract] [Full Text] [PDF]