Résumé :
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[BDSP. Notice produite par INIST-CNRS qR0xCAoE. Diffusion soumise à autorisation]. 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, 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 x 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 x 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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