title: 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.
authors.affiliation: a Department of Clinical Immunology , Aalborg University Hospital , Denmark.
authors.forename: Kaspar Rene
authors.initials: KR
authors.lastname: Nielsen
authors.affiliation: a Department of Clinical Immunology , Aalborg University Hospital , Denmark.
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: a Department of Clinical Immunology , Aalborg University Hospital , Denmark.
authors.forename: Thure Mors
authors.initials: TM
authors.lastname: Haunstrup
authors.affiliation: b Department of Haematology , Aalborg University Hospital.
authors.forename: Julie Støve
authors.initials: JS
authors.lastname: Bødker
authors.affiliation: b Department of Haematology , Aalborg University Hospital.|c Clinical Cancer Research Center, Aalborg University Hospital , Denmark and Department of Clinical Medicine , Aalborg University , Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Dybkær
authors.affiliation: a Department of Clinical Immunology , Aalborg University Hospital , Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Baech
authors.affiliation: b Department of Haematology , Aalborg University Hospital.|c Clinical Cancer Research Center, Aalborg University Hospital , Denmark and Department of Clinical Medicine , Aalborg University , Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Bøgsted
authors.affiliation: b Department of Haematology , Aalborg University Hospital.|c Clinical Cancer Research Center, Aalborg University Hospital , Denmark and Department of Clinical Medicine , Aalborg University , Denmark.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Johnsen
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007109:Immunity / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk
keywords: B-cell; SNP; immune response genes; lymphoma; outcome; susceptibility