Peer-Reviewed Journal Details
Mandatory Fields
Skibola C.;Bracci P.;Nieters A.;Brooks-Wilson A.;De Sanjosé S.;Hughes A.;Cerhan J.;Skibola D.;Purdue M.;Kane E.;Lan Q.;Foretova L.;Schenk M.;Spinelli J.;Slager S.;De Roos A.;Smith M.;Roman E.;Cozen W.;Boffetta P.;Kricker A.;Zheng T.;Lightfoot T.;Cocco P.;Benavente Y.;Zhang Y.;Hartge P.;Linet M.;Becker N.;Brennan P.;Zhang L.;Armstrong B.;Smith A.;Shiao R.;Novak A.;Maynadie M.;Chanock S.;Staines A.;Holford T.;Holly E.;Rothman N.;Wang S.
American Journal of Epidemiology
Tumor necrosis factor (TNF) and lymphotoxin-α (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium
Optional Fields
Lymphoma Lymphoma, non-Hodgkin Lymphotoxin-alpha Meta-analysis Polymorphism, genetic Polymorphism, single nucleotide Tumor necrosis factor-alpha
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.
Grant Details