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Tumor Necrosis Factor (TNF) and Lymphotoxin-alpha (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma in the InterLymph Consortium
Journal article   Open access   Peer reviewed

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

Christine F. Skibola, Paige M. Bracci, Alexandra Nieters, Angela Brooks-Wilson, Silvia de Sanjose, Ann Maree Hughes, James R. Cerhan, Danica R. Skibola, Mark Purdue, Eleanor Kane, …
American journal of epidemiology, v 171(3), pp 267-276
01 Feb 2010
PMID: 20047977
url
https://academic.oup.com/aje/article-pdf/171/3/267/405004/kwp383.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/aje/kwp383View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Public, Environmental & Occupational Health Science & Technology
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 (ORallelic) = 1.10, P-trend = 0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic = 1.23, P-trend = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: ORallelic = 1.13, P-trend = 0.0001; DLBCL: ORallelic = 1.25, P-trend = 3.7 x 10(-6); marginal zone lymphoma: ORallelic = 1.35, P-trend = 0.004) and LTA 252G carriers (DLBCL: ORallelic = 1.12, P-trend = 0.006; mycosis fungoides: ORallelic = 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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