Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium.
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Rothman Nathaniel, Skibola Christine F, Wang Sophia S, Morgan Gareth, Lan Qing, Smith Martyn T, Spinelli John J, Willett Eleanor, De Sanjose Silvia, Cocco Pierluigi, Berndt Sonja I, Brennan Paul, Brooks-Wilson Angela, Wacholder Sholom, Becker Nikolaus, Hartge Patricia, Zheng Tongzhang, Roman Eve, Holly Elizabeth A, Boffetta Paolo, Armstrong Bruce, Cozen Wendy, Linet Martha, Bosch F Xavier, Ennas Maria Grazia, Holford Theodore R, Gallagher Richard P, Rollinson Sara, Bracci Paige M, Cerhan James R, Whitby Denise, Moore Patrick S, Leaderer Brian, Lai Agnes, Spink Charlotte, Davis Scott, Bosch Ramon, Scarpa Aldo, Zhang Yawei, Severson Richard K, Yeager Meredith, Chanock Stephen, Nieters Alexandra
Аннотация
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 non-Hodgkin 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 IL10 -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.