Journal Article

A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

Mark P. Purdue, Qing Lan, Sophia S. Wang, Anne Kricker, Idan Menashe, Tong-Zhang Zheng, Patricia Hartge, Andrew E. Grulich, Yawei Zhang, Lindsay M. Morton, Claire M. Vajdic, Theodore R. Holford, Richard K. Severson, Brian P. Leaderer, James R. Cerhan, Meredith Yeager, Wendy Cozen, Kevin Jacobs, Scott Davis, Nathaniel Rothman, Stephen J. Chanock, Nilanjan Chatterjee and Bruce K. Armstrong

in Carcinogenesis

Volume 30, issue 2, pages 275-281
Published in print February 2009 | ISSN: 0143-3334
Published online November 2008 | e-ISSN: 1460-2180 | DOI:
A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma

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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 TLR10TLR1TLR6 gene cluster were genotyped. Two TLR10TLR1TLR6 variants in moderate linkage disequilibrium were significantly associated with NHL: rs10008492 [odds ratio for CT genotype (ORCT) 1.12, 95% confidence interval (CI) 0.97–1.30; ORTT 1.40, 95% CI 1.15–1.71; Ptrend = 0.001] and rs4833103 (ORAC 0.75, 95% CI 0.64–0.88; ORAA 0.74, 95% CI 0.62–0.90; Ptrend = 0.002; Pdominant = 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 (ORCT/CC 1.89, 95% CI 1.27–2.81; Pdominant = 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 TLR10TLR1TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

Journal Article.  5198 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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