Inherited variation in immune response genes in follicular lymphoma and diffuse large B-cell lymphoma

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.

Keywords::

• B-cell
• immune response genes
• lymphoma
• outcome
• SNP
• susceptibility

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.

Supplementary material available online

Supplementary Tables I and II