Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.
<h4>Background</h4>Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.<h4>Methods</h4>We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hod...
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doaj-5fca8bcbdb944f94b84bd0f4aedbec212021-03-04T07:23:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011010e013932910.1371/journal.pone.0139329Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.Kaspar René NielsenRudi SteffensenMette Dahl BendtsenMaria Rodrigo-DomingoJohn BaechThure Mors HaunstrupKim Steve BergkvistAlexander SchmitzJulie Stoeveve BoedkerPreben JohansenKaren DybkaeærMartin BoeøgstedHans Erik Johnsen<h4>Background</h4>Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.<h4>Methods</h4>We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included.<h4>Results</h4>We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02-0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center.<h4>Conclusions</h4>The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.https://doi.org/10.1371/journal.pone.0139329 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaspar René Nielsen Rudi Steffensen Mette Dahl Bendtsen Maria Rodrigo-Domingo John Baech Thure Mors Haunstrup Kim Steve Bergkvist Alexander Schmitz Julie Stoeveve Boedker Preben Johansen Karen Dybkaeær Martin Boeøgsted Hans Erik Johnsen |
spellingShingle |
Kaspar René Nielsen Rudi Steffensen Mette Dahl Bendtsen Maria Rodrigo-Domingo John Baech Thure Mors Haunstrup Kim Steve Bergkvist Alexander Schmitz Julie Stoeveve Boedker Preben Johansen Karen Dybkaeær Martin Boeøgsted Hans Erik Johnsen Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. PLoS ONE |
author_facet |
Kaspar René Nielsen Rudi Steffensen Mette Dahl Bendtsen Maria Rodrigo-Domingo John Baech Thure Mors Haunstrup Kim Steve Bergkvist Alexander Schmitz Julie Stoeveve Boedker Preben Johansen Karen Dybkaeær Martin Boeøgsted Hans Erik Johnsen |
author_sort |
Kaspar René Nielsen |
title |
Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. |
title_short |
Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. |
title_full |
Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. |
title_fullStr |
Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. |
title_full_unstemmed |
Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival. |
title_sort |
inherited inflammatory response genes are associated with b-cell non-hodgkin's lymphoma risk and survival. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
<h4>Background</h4>Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment.<h4>Methods</h4>We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included.<h4>Results</h4>We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02-0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center.<h4>Conclusions</h4>The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis. |
url |
https://doi.org/10.1371/journal.pone.0139329 |
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