Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

Hervé Ghesquières; Brian K Link; James R Cerhan; Matthew J Maurer; Ahmet Dogan; Olivier Casasnovas; Stephen M Ansell; Beth R Larrabee; Eva Lech-Maranda; Anne J Novak; Anne-Laure Borrel; Susan L Slager; Pauline Brice; Cristine Allmer; Annie Brion; Steven C Ziesmer; Franck Morschhauser; Thomas M Habermann; Isabelle Gaillard; Aspasia Stamatoullas; Christophe Fermé; William R Macon; Josée Audouin; Gilles Salles

doi:10.1016/j.cyto.2013.08.002

Back

Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

Journal article

Peer reviewed

Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts

Hervé Ghesquières, Brian K Link, James R Cerhan, Matthew J Maurer, Ahmet Dogan, Olivier Casasnovas, Stephen M Ansell, Beth R Larrabee, Eva Lech-Maranda, Anne J Novak, …

Cytokine (Philadelphia, Pa.), Vol.64(2), pp.523-531

11/2013

DOI: 10.1016/j.cyto.2013.08.002

PMCID: PMC4017856

PMID: 24008079

Files and links (1)

url

http://doi.org/10.1016/j.cyto.2013.08.002View

Open Access

Abstract

•Cytokines are important immune mediators in classical Hodgkin lymphoma.•SNPs in cytokine genes could influence cytokine production.•IL10, TNFA, IL6, IL1RN, INFG, CCL17 SNPs were not associated with cytokine levels.•Overall, none of these SNPs influence progression-free survival of CHL patients.•In analysis by EBV status, TNFA−308G>A influenced prognosis of EBV negative CHL. Cytokines are important immune mediators of classical Hodgkin lymphoma (CHL) pathogenesis, and circulating levels at diagnosis may help predict prognosis. Germline single nucleotide polymorphisms (SNPs) in immune genes have been correlated with cytokine production and function. We investigated whether selected germline SNPs in IL10 (rs1800890, rs1800896, rs1800871, rs1800872), TNFA (rs1800629), IL6 (rs1800795), ILRN (rs419598), INFG (rs2430561) and CCL17 (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, N=464; median age=32years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=239; median age=38years); 22% of 346 CHL cases with EBV tumor status were positive. There was no association with any of the SNPs with cytokine levels. Overall, there was no association of any of the SNPs with PFS. In exploratory analyses by EBV status, TNFA rs1800629 (HRAA/AG=2.41; 95%CI, 1.17–4.94) was associated with PFS in EBV-negative GELA patients, with similar trends in the SPORE patients (HRAA/AG=1.63; 95%CI, 0.61–4.40). In a meta-analysis of the two studies, TNFA (HRAA/AG=2.11; 95%CI, 1.18–3.77; P=0.01) was statistically significant, and further adjustment for the international prognostic system did not alter this result. This study showed that germline variation in TNFA was associated with CHL prognosis for EBV-negative patients, which will require confirmation. These results support broader studies on the differential impact of genetic variation in immune genes on EBV-positive vs. EBV-negative CHL pathogenesis.

Cytokines

EBV

TNFA

Hodgkin lymphoma

Polymorphism

Details

Title: Subtitle: Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts
Creators: Hervé Ghesquières - Onco-Hematology, Centre Léon Bérard, UMR CNRS 5239, Université Lyon 1, Lyon, France
Brian K Link - University of Iowa, Holden Comprehensive Cancer Center, Iowa City, IA, USA
James R Cerhan - Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Matthew J Maurer - Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Ahmet Dogan - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Olivier Casasnovas - Department of Hematology, CHU Dijon, Dijon, France
Stephen M Ansell - Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Beth R Larrabee - Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Eva Lech-Maranda - Department of Hematology, Warsaw, Poland
Anne J Novak - Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Anne-Laure Borrel - UMR CNRS 5239, Université Lyon 1, Lyon, France
Susan L Slager - Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Pauline Brice - Department of Hematology, APHP, Hôpital Saint Louis, Paris, France
Cristine Allmer - Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Annie Brion - Department of Hematology, CHU de Besançon, France
Steven C Ziesmer - Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Franck Morschhauser - Department of Hematology, CHU, Lille, France
Thomas M Habermann - Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Isabelle Gaillard - Unité Hémopathies lymphoïdes, Hôpital Henri Mondor, Créteil, France
Aspasia Stamatoullas - Department of Hematology, Centre Henri Becquerel, Rouen, France
Christophe Fermé - Department of Hematology, Institut Gustave Roussy, Villejuif, France
William R Macon - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Josée Audouin - Department of Pathology, APHP, Hôtel Dieu, Paris, France
Gilles Salles - Department of Hematology, UMR CNRS 5239, Université Lyon 1, HCL, Pierre-Bénite, France
Resource Type: Journal article
Publication Details: Cytokine (Philadelphia, Pa.), Vol.64(2), pp.523-531
DOI: 10.1016/j.cyto.2013.08.002
PMID: 24008079
PMCID: PMC4017856
NLM abbreviation: Cytokine
ISSN: 1043-4666
eISSN: 1096-0023
Publisher: Elsevier Ltd
Language: English
Date published: 11/2013
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984094391102771

Metrics

13 Record Views

13 Times Cited - Web of Science