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

Tumor Necrosis Factor (TNF) and Lymphotoxin- (LTA) Polymorphisms and Risk of Non-Hodgkin Lymphoma... 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- (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, Ptrend0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic1.23, Ptrend0.004). In the combined population, odds ratios were increased for TNF 308A carriers (NHL: ORallelic1.13, Ptrend0.0001; DLBCL: ORallelic1.25, Ptrend3.7 106; marginal zone lymphoma: ORallelic1.35, Ptrend0.004) and LTA 252G carriers (DLBCL: ORallelic1.12, Ptrend 0.006; mycosis fungoides: ORallelic1.44, Ptrend0.015). The LTA 252A>G/TNF 308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P2.9 108). Results suggested associations between IL10 3575T>A and DLBCL (Ptrend0.02) and IL10 1082A>G and mantle cell lymphoma (Ptrend0.04). 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Epidemiology Oxford University Press

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References (38)

Publisher
Oxford University Press
Copyright
American Journal of Epidemiology Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2010.
ISSN
0002-9262
eISSN
1476-6256
DOI
10.1093/aje/kwp383
pmid
20047977
Publisher site
See Article on Publisher Site

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- (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, Ptrend0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic1.23, Ptrend0.004). In the combined population, odds ratios were increased for TNF 308A carriers (NHL: ORallelic1.13, Ptrend0.0001; DLBCL: ORallelic1.25, Ptrend3.7 106; marginal zone lymphoma: ORallelic1.35, Ptrend0.004) and LTA 252G carriers (DLBCL: ORallelic1.12, Ptrend 0.006; mycosis fungoides: ORallelic1.44, Ptrend0.015). The LTA 252A>G/TNF 308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P2.9 108). Results suggested associations between IL10 3575T>A and DLBCL (Ptrend0.02) and IL10 1082A>G and mantle cell lymphoma (Ptrend0.04). 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.

Journal

American Journal of EpidemiologyOxford University Press

Published: Jan 4, 2010

Keywords: lymphoma lymphoma, non-Hodgkin lymphotoxin-alpha meta-analysis polymorphism, genetic polymorphism, single nucleotide tumor necrosis factor-alpha

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