title: Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.
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-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.
authors.affiliation: 237A Hildebrand Hall, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-7360, USA. chrisfs@berkeley.edu
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
authors.forename: Paige M
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authors.lastname: Bracci
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authors.lastname: Nieters
authors.forename: Angela
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authors.lastname: Brooks-Wilson
authors.forename: Silvia
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authors.lastname: de Sanjosé
authors.forename: Ann Maree
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authors.lastname: Hughes
authors.forename: James R
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authors.lastname: Cerhan
authors.forename: Danica R
authors.initials: DR
authors.lastname: Skibola
authors.forename: Mark
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authors.lastname: Purdue
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authors.forename: Qing
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authors.lastname: Foretova
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authors.lastname: Schenk
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authors.forename: Susan L
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authors.lastname: Slager
authors.forename: Anneclaire J
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authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
authors.forename: Eve
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authors.lastname: Roman
authors.forename: Wendy
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authors.lastname: Cozen
authors.forename: Paolo
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authors.lastname: Boffetta
authors.forename: Anne
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authors.lastname: Kricker
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Tracy
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authors.lastname: Lightfoot
authors.forename: Pierluigi
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authors.lastname: Cocco
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Yawei
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authors.lastname: Zhang
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Martha S
authors.initials: MS
authors.lastname: Linet
authors.forename: Nikolaus
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authors.lastname: Becker
authors.forename: Paul
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authors.lastname: Brennan
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Bruce
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authors.lastname: Armstrong
authors.forename: Alex
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authors.lastname: Smith
authors.forename: Renee
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authors.lastname: Shiao
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Marc
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authors.lastname: Maynadie
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Anthony
authors.initials: A
authors.lastname: Staines
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holly
authors.forename: Nathaniel
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authors.lastname: Rothman
authors.forename: Sophia S
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authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000208:ethnology; D002170:Canada / Q000208:ethnology; D016022:Case-Control Studies; D005060:Europe / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D007390:International Agencies; D008228:Lymphoma, Non-Hodgkin / Q000208:ethnology / Q000235:genetics*; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014481:United States / Q000208:ethnology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10