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 RothmanStephen J. Chanock, Nilanjan Chatterjee, Bruce K. Armstrong

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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 (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 TLR10-TLR1-TLR6 region is associated with NHL risk and suggests that TLR2 variants may influence susceptibility to MZL.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalCarcinogenesis
Volume30
Issue number2
DOIs
StatePublished - Feb 19 2009

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Purdue, M. P., Lan, Q., Wang, S. S., Kricker, A., Menashe, I., Zheng, T. Z., Hartge, P., Grulich, A. E., Zhang, Y., Morton, L. M., Vajdic, C. M., Holford, T. R., Severson, R. K., Leaderer, B. P., Cerhan, J. R., Yeager, M., Cozen, W., Jacobs, K., Davis, S., ... Armstrong, B. K. (2009). A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis, 30(2), 275-281. https://doi.org/10.1093/carcin/bgn262