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Publication Detail

Title: Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.

Authors: Skibola, Christine F; Bracci, Paige M; Nieters, Alexandra; Brooks-Wilson, Angela; de Sanjosé, Silvia; Hughes, Ann Maree; Cerhan, James R; Skibola, Danica R; Purdue, Mark; Kane, Eleanor; Lan, Qing; Foretova, Lenka; Schenk, Maryjean; Spinelli, John J; Slager, Susan L; De Roos, Anneclaire J; Smith, Martyn T; Roman, Eve; Cozen, Wendy; Boffetta, Paolo; Kricker, Anne; Zheng, Tongzhang; Lightfoot, Tracy; Cocco, Pierluigi; Benavente, Yolanda; Zhang, Yawei; Hartge, Patricia; Linet, Martha S; Becker, Nikolaus; Brennan, Paul; Zhang, Luoping; Armstrong, Bruce; Smith, Alex; Shiao, Renee; Novak, Anne J; Maynadie, Marc; Chanock, Stephen J; Staines, Anthony; Holford, Theodore R; Holly, Elizabeth A; Rothman, Nathaniel; Wang, Sophia S

Published In Am J Epidemiol, (2010 Feb 01)

Abstract: 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.

PubMed ID: 20047977 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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