Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk.
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.
Nieters
A
A
Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany. a.nieters@dkfz.de
Beckmann
L
L
Deeg
E
E
Becker
N
N
D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D008223:Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051193:Toll-Like Receptors / Q000235:genetics*
D053709:Interleukin-10 Receptor alpha Subunit; D051193:Toll-Like Receptors; D016753:Interleukin-10