6533b831fe1ef96bd1299012

RESEARCH PRODUCT

Tumor necrosis factor (TNF) and lymphotoxin-a (LTA) polymorphisms and risk of non-hodgkin lymphoma in the interLymph consortium

Silvia De SanjoséEve RomanAnneclaire J. De RoosBruce K. ArmstrongMarc MaynadiéMark P. PurdueLuoping ZhangYawei ZhangJohn J. SpinelliStephen J. ChanockAnn Maree HughesTongzhang ZhengTongzhang ZhengA NietersAngela Brooks-wilsonAngela Brooks-wilsonWendy CozenEleanor KaneAnne J. NovakNikolaus BeckerMartha S. LinetAnne KrickerRenee ShiaoQing LanQing LanNathaniel RothmanYolanda BenaventePaul BrennanAlex SmithTracy LightfootAnthony StainesMartyn T. SmithPaolo BoffettaMaryjean SchenkElizabeth A. HollyChristine F. SkibolaSusan L. SlagerPaige M. BracciJames R. CerhanPierluigi CoccoPatricia HartgeDanica R. SkibolaLenka ForetovaSophia S. WangTheodore R. Holford

subject

MaleEpidemiologyTNFGastroenterology0302 clinical medicineRisk Factorsimmune system diseaseshemic and lymphatic diseasesAged 80 and over0303 health scienceseducation.field_of_studyLymphoma Non-Hodgkinnon-Hodgkin lymphomaMiddle Aged3. Good healthInterleukin-10EuropeLTA030220 oncology & carcinogenesisFemaleLymphotoxin alphaAdultmedicine.medical_specialtyCanadaAdolescentTumor necrosis factorMeta- and Pooled AnalysesPopulationPolymorphism Single NucleotideWhite People03 medical and health sciencesYoung AdultInternal medicinemedicineHumansGenetic Predisposition to Diseaseeducation030304 developmental biologyAgedMycosis fungoidesbusiness.industryTumor Necrosis Factor-alphaAustraliaInternational AgenciesInterLymph ConsortiumOdds ratiomedicine.diseaseUnited StatesNon-Hodgkin's lymphomaLymphomaCase-Control StudiesImmunologyMantle cell lymphomalymphotoxin-alphabusinessDiffuse large B-cell lymphoma

description

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.

yearjournalcountryeditionlanguage
2010-01-04
10.1093/aje/kwp383http://hdl.handle.net/11585/682491