title: A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma.
abstract: 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.
authors.affiliation: 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
authors.forename: Mark P
authors.initials: MP
authors.lastname: Purdue
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: Tong-Zhang
authors.initials: TZ
authors.lastname: Zheng
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Brian P
authors.initials: BP
authors.lastname: Leaderer
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Kevin
authors.initials: K
authors.lastname: Jacobs
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
mesh_terms: 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*
chemical_list: D051193:Toll-Like Receptors