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, À2, À4, À5, À9, IL10 and IL10 receptor (IL10RA). The IL10RA Ser138Gly variant was underrepresented among lymphoma cases (odds ratio (OR) ¼ 0.81, 95 per cent confidence interval (95% CI) ¼ 0.65-1.02), mainly owing to an inverse association with Hodgkin's lymphoma (HL). The TLR2 À16933T4A variant was associated with a 2.8-fold increased risk of follicular lymphoma (95% CI ¼ 1.43-5.59) and a decreased risk of chronic lymphocytic leukaemia (OR ¼ 0.61, 95% CI ¼ 0.38-0.95). Furthermore, the TLR4 Asp299Gly variant was positively associated with the risk of mucosa-associated lymphoid tissue lymphoma (OR ¼ 2.76, 95% CI ¼ 1.12-6.81) and HL (OR ¼ 1.80, 95% CI ¼ 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.

BackgroundWe aimed at identifying variables predicting hypoglycemia in elderly type 2 diabetic patients and the relation to HbA1c values achieved.DesignProspective, observational registry in 3810 patients in primary care. Comparison of patients in different age tertiles: with an age < 60 (young, n=1,253), age 60 to < 70 (middle aged, n=1,184) to those ≥ 70 years (elderly, n=1,373). Odds Ratios (OR) with 95% confidence intervals (CI) were determined from univariable and multivariable regression analyses.ResultsElderly patients had a later diabetes diagnosis, a longer diabetes duration, better glucose control and more frequent co-morbid disease conditions. Overall 10.7% of patients experienced any severity hypoglycemia within the last 12 months prior to inclusion. Higher rates of hypoglycemia were observed in the elderly than in the young after adjusting for differences in HbA1c, fasting and post-prandial blood glucose (OR 1.68; 95%CI 1.16-2.45). This was particularly true for hypoglycemic episodes without specific symptoms (OR 1.74; 95%CI 1.05-2.89). In a multivariate model stroke / transitory ischemic attack, the presence of heart failure, clinically relevant depression, sulfonylurea use and blood glucose self-measurement were associated with hypoglycemic events.ConclusionElderly patients are at an increased risk of hypoglycemia even at comparable glycemic control. Therefore identified variables associated with hypoglycemia in the elderly such as heart failure, clinically relevant depression, the use of sulfonylurea help to optimize the balance between glucose control and low levels of hypoglycemia. Asymptomatic hypoglycemia should not be disregarded as irrelevant but considered as a sign of possible hypoglycemia associated autonomic failure.

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