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Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk

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.

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Acknowledgements

We thank the participants of the study and the many colleagues who supported the performance of the study. A detailed list is presented in previous publications.5, 8 Furthermore, we thank Marlen Auer, Bettina Ehret and Georg Zahn for excellent technical assistance. The study was funded by the Federal Office for Radiation Protection (StSch4261 and StSch4420). The European Community supported the set up of a common protocol for assessment of occupational exposures (SOC 98 201307 05F02) and implementation of additional study areas (QLK4-CT-2000-00422). Genotyping was supported by the German José Carreras Leukaemia foundation (DJCLS_R04/08). This work was supported by a Deutsche Forschungsgemeinschaft Grant CH117/3-1 (LB).

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Correspondence to A Nieters.

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Nieters, A., Beckmann, L., Deeg, E. et al. Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun 7, 615–624 (2006). https://doi.org/10.1038/sj.gene.6364337

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