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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) inTLR2,TLR4and theTLR10–TLR1–TLR6gene cluster were genotyped. TwoTLR10–TLR1–TLR6variants 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; ORTT1.40, 95% CI 1.15–1.71;P  trend = 0.001] and rs4833103 (ORAC0.75, 95% CI 0.64–0.88; ORAA0.74, 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 betweenTLR2variation and all NHL, although the rare variant rs3804100 was significantly associated with marginal zone lymphoma (MZL), both overall (ORCT/CC1.89, 95% CI 1.27–2.81;P  dominant = 0.002) and in two of the three studies. No associations withTLR4variants were observed. This pooled analysis provides strong evidence that variation in theTLR10–TLR1–TLR6region is associated with NHL risk and suggests thatTLR2variants may influence susceptibility to MZL.

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