A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma.
Toll-like receptors (TLRs) may influence the development of non-Hodgkin lymphoma (NHL) given their important roles in recognizing microbial pathogens and stimulating multiple immune pathways. We conducted an investigation of TLR gene variants in a pooled analysis including three population-based case-control studies of NHL (1946 cases and 1808 controls). Thirty-six tag single-nucleotide polymorphisms (SNPs) in TLR2, TLR4 and the TLR10-TLR1-TLR6 gene cluster were genotyped. Two TLR10-TLR1-TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (OR(CT)) 1.12, 95% confidence interval (CI) 0.97-1.30; OR(TT) 1.40, 95% CI 1.15-1.71; P(trend) = 0.001] and rs4833103 (OR(AC) 0.75, 95% CI 0.64-0.88; OR(AA) 0.74, 95% CI 0.62-0.90; P(trend) = 0.002; P(dominant) = 0.0002). Associations with these SNPs were consistent across all the three studies and did not appreciably differ by histologic subtype. We found little evidence of association between TLR2 variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (OR(CT/CC) 1.89, 95% CI 1.27-2.81; P(dominant) = 0.002) and in two of the three studies. No associations with TLR4 variants were observed. This pooled analysis provides strong evidence that variation in the TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.
Purdue
Mark P
MP
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20892, USA. purduem@mail.nih.gov
Lan
Qing
Q
Wang
Sophia S
SS
Kricker
Anne
A
Menashe
Idan
I
Zheng
Tong-Zhang
TZ
Hartge
Patricia
P
Grulich
Andrew E
AE
Zhang
Yawei
Y
Morton
Lindsay M
LM
Vajdic
Claire M
CM
Holford
Theodore R
TR
Severson
Richard K
RK
Leaderer
Brian P
BP
Cerhan
James R
JR
Yeager
Meredith
M
Cozen
Wendy
W
Jacobs
Kevin
K
Davis
Scott
S
Rothman
Nathaniel
N
Chanock
Stephen J
SJ
Chatterjee
Nilanjan
N
Armstrong
Bruce K
BK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D051193:Toll-Like Receptors / Q000235:genetics*
D051193:Toll-Like Receptors