Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.
BACKGROUND
Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph).


METHODS
We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model.


RESULTS
The tumour necrosis factor (TNF) -308G-->A polymorphism was associated with increased risk of non-Hodgkin lymphoma (p for trend=0.005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1.29 [95% CI 1.10-1.51] for GA and 1.65 [1.16-2.34] for AA, p for trend <0.0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T-->A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0.02), again particularly for diffuse large B-cell lymphoma (p for trend=0.006). For individuals homozygous for the TNF -308A allele and carrying at least one IL10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2.13 [1.37-3.32], p=0.00083).


CONCLUSIONS
Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.
Rothman
Nathaniel
N
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. rothmann@mail.nih.gov
Skibola
Christine F
CF
Wang
Sophia S
SS
Morgan
Gareth
G
Lan
Qing
Q
Smith
Martyn T
MT
Spinelli
John J
JJ
Willett
Eleanor
E
De Sanjose
Silvia
S
Cocco
Pierluigi
P
Berndt
Sonja I
SI
Brennan
Paul
P
Brooks-Wilson
Angela
A
Wacholder
Sholom
S
Becker
Nikolaus
N
Hartge
Patricia
P
Zheng
Tongzhang
T
Roman
Eve
E
Holly
Elizabeth A
EA
Boffetta
Paolo
P
Armstrong
Bruce
B
Cozen
Wendy
W
Linet
Martha
M
Bosch
F Xavier
FX
Ennas
Maria Grazia
MG
Holford
Theodore R
TR
Gallagher
Richard P
RP
Rollinson
Sara
S
Bracci
Paige M
PM
Cerhan
James R
JR
Whitby
Denise
D
Moore
Patrick S
PS
Leaderer
Brian
B
Lai
Agnes
A
Spink
Charlotte
C
Davis
Scott
S
Bosch
Ramon
R
Scarpa
Aldo
A
Zhang
Yawei
Y
Severson
Richard K
RK
Yeager
Meredith
M
Chanock
Stephen
S
Nieters
Alexandra
A
D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10