Tumor Necrosis Factor (TNF) and Lymphotoxin- (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium | Zendy

Christine F. Skibola | Zendy; Paige M. Bracci | Zendy; A. Nieters | Zendy; Angela BrooksWilson | Zendy; Sílvia de Sanjosé | Zendy; Ann M. Hughes | Zendy; James R. Cerhan | Zendy; Danica R. Skibola | Zendy; Mark P. Purdue | Zendy; Eleanor Kane | Zendy; Qing Lan | Zendy; Lenka Foretová | Zendy; Michael Schenk | Zendy; John J. Spinelli | Zendy; Susan L. Slager | Zendy; Anneclaire J. De Roos | Zendy; Martyn T. Smith | Zendy; Eve Roman | Zendy; Wendy Cozen | Zendy; P. Boffetta | Zendy; Anne Kricker | Zendy; T. Zheng | Zendy; T. Lightfoot | Zendy; Pier Luigi Cocco | Zendy; Yolanda Benavente | Zendy; Y. Zhang | Zendy; Patricia Hartge | Zendy; Martha S. Linet | Zendy; N. Becker | Zendy; Paul Brennan | Zendy; Liling Zhang | Zendy; Bruce K. Armstrong | Zendy; A. G. Smith | Zendy; Renee Shiao | Zendy; Anne J. Novak | Zendy; M. Maynadié | Zendy; Stephen J. Chanock | Zendy; Anthony Staines | Zendy; Theodore R. Holford | Zendy; Elizabeth A. Holly | Zendy; Nathaniel Rothman | Zendy; Sophia Wang | Zendy

Open Access

Tumor Necrosis Factor (TNF) and Lymphotoxin- (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium

Author(s) -

Christine F. Skibola,

Paige M. Bracci,

A. Nieters,

Angela BrooksWilson,

Sílvia de Sanjosé,

Ann M. Hughes,

James R. Cerhan,

Danica R. Skibola,

Mark P. Purdue,

Eleanor Kane,

Qing Lan,

Lenka Foretová,

Michael Schenk,

John J. Spinelli,

Susan L. Slager,

Anneclaire J. De Roos,

Martyn T. Smith,

Eve Roman,

Wendy Cozen,

P. Boffetta,

Anne Kricker,

T. Zheng,

T. Lightfoot,

Pier Luigi Cocco,

Yolanda Benavente,

Y. Zhang,

Patricia Hartge,

Martha S. Linet,

N. Becker,

Paul Brennan,

Liling Zhang,

Bruce K. Armstrong,

A. G. Smith,

Renee Shiao,

Anne J. Novak,

M. Maynadié,

Stephen J. Chanock,

Anthony Staines,

Theodore R. Holford,

Elizabeth A. Holly,

Nathaniel Rothman,

Sophia Wang

Publication year - 2010

Publication title -

american journal of epidemiology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.33

H-Index - 256

eISSN - 1476-6256

pISSN - 0002-9262

DOI - 10.1093/aje/kwp383

Subject(s) - odds ratio , lymphotoxin alpha , medicine , immunology , haplotype , lymphoma , oncology , tumor necrosis factor alpha , gastroenterology , lymphotoxin , biology , allele , genetics , gene

In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.

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