Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium
Date
2010
Authors
Skibola, Christine F
Bracci, Paige M
Nieters, Alexander
Brooks-Wilson, Angela
de Sanjose, Silvia
Hughes, Ann Maree
Cerhan, James R
Skibola, Danica R
Purdue, Mark
Kane, Eleanor
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Oxford University Press
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-α (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, Ptrend=0.001; diffuse large B-cell lymphoma (DLBCL): ORallelic=1.23, Ptrend=0.004). In the combined population, odds ratios were increased for TNF-308A carriers (NHL: ORallelic=1.13, Ptrend=0.0001; DLBCL: ORallelic=1.25, Ptrend=3.7 × 10-6; marginal zone lymphoma: ORallelic=1.35, Ptrend=0.004) and LTA 252G carriers (DLBCL: ORallelic=1.12, Ptrend = 0.006; mycosis fungoides: ORallelic=1.44, Ptrend=0.015). The LTA 252A>G/TNF-308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P=2.9 × 10-8). Results suggested associations between IL10-3575T>A and DLBCL (Ptrend=0.02) and IL10-1082A>G and mantle cell lymphoma (Ptrend=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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Keywords
Keywords: caspase recruitment domain protein 15; interleukin 10; lymphotoxin; tumor necrosis factor; ethnic group; etiology; gene expression; health risk; meta-analysis; protein; toxin; tumor; adult; article; controlled study; ethnicity; female; genetic variability Lymphoma; Lymphoma, non-Hodgkin; Lymphotoxin-alpha; Meta-analysis; Polymorphism, genetic; Polymorphism, single nucleotide; Tumor necrosis factor-alpha
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Source
American Journal of Epidemiology
Type
Journal article
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2037-12-31
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