Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.
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.
Skibola
Christine F
CF
237A Hildebrand Hall, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-7360, USA. chrisfs@berkeley.edu
Bracci
Paige M
PM
Nieters
Alexandra
A
Brooks-Wilson
Angela
A
de Sanjosé
Silvia
S
Hughes
Ann Maree
AM
Cerhan
James R
JR
Skibola
Danica R
DR
Purdue
Mark
M
Kane
Eleanor
E
Lan
Qing
Q
Foretova
Lenka
L
Schenk
Maryjean
M
Spinelli
John J
JJ
Slager
Susan L
SL
De Roos
Anneclaire J
AJ
Smith
Martyn T
MT
Roman
Eve
E
Cozen
Wendy
W
Boffetta
Paolo
P
Kricker
Anne
A
Zheng
Tongzhang
T
Lightfoot
Tracy
T
Cocco
Pierluigi
P
Benavente
Yolanda
Y
Zhang
Yawei
Y
Hartge
Patricia
P
Linet
Martha S
MS
Becker
Nikolaus
N
Brennan
Paul
P
Zhang
Luoping
L
Armstrong
Bruce
B
Smith
Alex
A
Shiao
Renee
R
Novak
Anne J
AJ
Maynadie
Marc
M
Chanock
Stephen J
SJ
Staines
Anthony
A
Holford
Theodore R
TR
Holly
Elizabeth A
EA
Rothman
Nathaniel
N
Wang
Sophia S
SS
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
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10