¹Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany

Correspondence: Dr A Nieters, Division of Clinical Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. E-mail: a.nieters@dkfz.de

Received 24 May 2006; Revised 5 July 2006; Accepted 24 July 2006; Published online 14 September 2006.

Abstract

Interactions between environment and immune system play an essential role in the aetiology of immunopathologies, including lymphomas. Toll-like receptors (TLR) belong to a group of pattern recognition receptors, with importance for innate immune response and inflammatory processes. Interleukin-10 (IL-10) is a key regulatory cytokine and has been implicated in lymphomagenesis. Functional polymorphisms in these inflammation-associated genes may affect the susceptibility towards lymphoma. To test this hypothesis, we have genotyped DNA of 710 lymphoma cases and 710 controls within the context of a population-based epidemiological study for 11 functionally important single-nucleotide polymorphisms in TLR1, -2, -4, -5, -9, IL10 and IL10 receptor (IL10RA). The IL10RA Ser138Gly variant was underrepresented among lymphoma cases (odds ratio (OR)=0.81, 95 per cent confidence interval (95% CI)=0.65–1.02), mainly owing to an inverse association with Hodgkin's lymphoma (HL). The TLR2 -16933T>A variant was associated with a 2.8-fold increased risk of follicular lymphoma (95% CI=1.43–5.59) and a decreased risk of chronic lymphocytic leukaemia (OR=0.61, 95% CI=0.38–0.95). Furthermore, the TLR4 Asp299Gly variant was positively associated with the risk of mucosa-associated lymphoid tissue lymphoma (OR=2.76, 95% CI=1.12–6.81) and HL (OR=1.80, 95% CI=0.99–3.26). In conclusion, this study suggests an effect of polymorphisms in factors of the innate immune response in the aetiology of some lymphoma subtypes.