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Abstract
Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) both depend on immune-mediated survival and proliferation signals from the tumor microenvironment. Inherited genetic variation influences this complex interaction. A total of 89 studies investigating immune-response genes in DLBCL and FL were critically reviewed. Relatively consistent association exists for variation in the tumor necrosis factor alpha (TNFA) and interleukin-10 loci and DLBCL risk; for DLBCL outcome association with the TNFA locus exists. Variations at chromosome 6p31-32 were associated with FL risk. Importantly, individual risk alleles have been shown to interact with each other. We suggest that the pathogenetic impact of polymorphic genes should include gene-gene interaction analysis and should be validated in preclinical model systems of normal B lymphopoiesis and B-cell malignancies. In the future, large cohort studies of interactions and genome-wide association studies are needed to extend the present findings and explore new risk alleles to be studied in preclinical models.
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
This study was supported by research funding from the EU 6th FP to MSCNET [LSHC-CT-2006-037602], the Danish Cancer Society, the Danish Research Agency to CHEPRE [#2101-07-0007] and the KE Jensen Foundation (2006–2014) to HEJ, MB and KD.