Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium

Background Common genetic variants in immune and inflammatory response genes can affect the risk of developing non-Hodgkin lymphoma. We aimed to test this hypothesis using previously unpublished data from eight European, Canadian, and US case-control studies of the International Lymphoma Epidemiology Consortium (InterLymph). Methods We selected 12 single-nucleotide polymorphisms for analysis, on the basis of previous functional or association data, in nine genes that have important roles in lymphoid development, Th1/Th2 balance, and proinflammatory or anti-inflammatory pathways (IL1A, IL1RN, IL1B, IL2, IL6, IL10, TNF, LTA, and CARD15). Genotype data for one or more single-nucleotide polymorphisms were available for 3586 cases of non-Hodgkin lymphoma and for 4018 controls, and were assessed in a pooled analysis by use of a random-effects logistic regression model. Findings The tumour necrosis factor (TNF) -308G -> A polymorphism was associated with increased risk of nonHodgkin lymphoma (p for trend=0 . 005), particularly for diffuse large B-cell lymphoma, the main histological subtype (odds ratio 1 . 29 [95% CI 1 . 10-1 . 51] for GA and 1.65 [1 . 16-2 . 34] for AA, p for trend < 0 . 0001), but not for follicular lymphoma. The interleukin 10 (IL10) -3575T -> A polymorphism was also associated with increased risk of non-Hodgkin lymphoma (p for trend=0 . 02), again particularly for diffuse large B-cell lymphoma (p for trend=0 . 006). For individuals homozygous for the TNF -308A allele and carrying at least one IL 10 -3575A allele, risk of diffuse large B-cell lymphoma doubled (2 . 13 [1 . 37-3 . 32], p=0 . 00083). Interpretation Common polymorphisms in TNF and IL10, key cytokines for the inflammatory response and Th1/Th2 balance, could be susceptibility loci for non-Hodgkin lymphoma. Moreover, our results underscore the importance of consortia for investigating the genetic basis of chronic diseases like cancer.