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

Hervé Ghesquières, Matthew J. Maurer, Olivier Casasnovas, Stephen Maxted 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 Matthew Habermann, Isabelle Gaillard, Brian K. Link, Aspasia Stamatoullas, Christophe Fermé, Ahmet DoganWilliam R. Macon, Josée Audouin, James R Cerhan, Gilles Salles

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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. =. 32. years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=. 239; median age. =. 38. years); 22% of 346 CHL cases with EBV tumor status were positive. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)523-531
Number of pages9
JournalCytokine
Volume64
Issue number2
DOIs
StatePublished - Nov 2013

Fingerprint

Polymorphism
Human Herpesvirus 4
Hodgkin Disease
Disease-Free Survival
Nucleotides
Genes
Cytokines
Single Nucleotide Polymorphism
Interleukin-10
Tumors
Interleukin-6
Research
France
Meta-Analysis
Neoplasms

Keywords

  • Cytokines
  • EBV
  • Hodgkin lymphoma
  • Polymorphism
  • TNFA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

Cite this

Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status : Results from two independent cohorts. / Ghesquières, Hervé; Maurer, Matthew J.; Casasnovas, Olivier; Ansell, Stephen Maxted; Larrabee, Beth R.; Lech-Maranda, Eva; Novak, Anne J; Borrel, Anne Laure; Slager, Susan L; Brice, Pauline; Allmer, Cristine; Brion, Annie; Ziesmer, Steven C.; Morschhauser, Franck; Habermann, Thomas Matthew; Gaillard, Isabelle; Link, Brian K.; Stamatoullas, Aspasia; Fermé, Christophe; Dogan, Ahmet; Macon, William R.; Audouin, Josée; Cerhan, James R; Salles, Gilles.

In: Cytokine, Vol. 64, No. 2, 11.2013, p. 523-531.

Research output: Contribution to journalArticle

Ghesquières, H, Maurer, MJ, Casasnovas, O, Ansell, SM, Larrabee, BR, Lech-Maranda, E, Novak, AJ, Borrel, AL, Slager, SL, Brice, P, Allmer, C, Brion, A, Ziesmer, SC, Morschhauser, F, Habermann, TM, Gaillard, I, Link, BK, Stamatoullas, A, Fermé, C, Dogan, A, Macon, WR, Audouin, J, Cerhan, JR & Salles, G 2013, 'Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status: Results from two independent cohorts', Cytokine, vol. 64, no. 2, pp. 523-531. https://doi.org/10.1016/j.cyto.2013.08.002
Ghesquières, Hervé ; Maurer, Matthew J. ; Casasnovas, Olivier ; Ansell, Stephen Maxted ; Larrabee, Beth R. ; Lech-Maranda, Eva ; Novak, Anne J ; Borrel, Anne Laure ; Slager, Susan L ; Brice, Pauline ; Allmer, Cristine ; Brion, Annie ; Ziesmer, Steven C. ; Morschhauser, Franck ; Habermann, Thomas Matthew ; Gaillard, Isabelle ; Link, Brian K. ; Stamatoullas, Aspasia ; Fermé, Christophe ; Dogan, Ahmet ; Macon, William R. ; Audouin, Josée ; Cerhan, James R ; Salles, Gilles. / Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status : Results from two independent cohorts. In: Cytokine. 2013 ; Vol. 64, No. 2. pp. 523-531.
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abstract = "Background: 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. Methods: 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. =. 32. years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=. 239; median age. =. 38. years); 22{\%} of 346 CHL cases with EBV tumor status were positive. Results: 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. Conclusions: 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.",
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T1 - Cytokine gene polymorphisms and progression-free survival in classical Hodgkin lymphoma by EBV status

T2 - Results from two independent cohorts

AU - Ghesquières, Hervé

AU - Maurer, Matthew J.

AU - Casasnovas, Olivier

AU - Ansell, Stephen Maxted

AU - Larrabee, Beth R.

AU - Lech-Maranda, Eva

AU - Novak, Anne J

AU - Borrel, Anne Laure

AU - Slager, Susan L

AU - Brice, Pauline

AU - Allmer, Cristine

AU - Brion, Annie

AU - Ziesmer, Steven C.

AU - Morschhauser, Franck

AU - Habermann, Thomas Matthew

AU - Gaillard, Isabelle

AU - Link, Brian K.

AU - Stamatoullas, Aspasia

AU - Fermé, Christophe

AU - Dogan, Ahmet

AU - Macon, William R.

AU - Audouin, Josée

AU - Cerhan, James R

AU - Salles, Gilles

PY - 2013/11

Y1 - 2013/11

N2 - Background: 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. Methods: 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. =. 32. years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=. 239; median age. =. 38. years); 22% of 346 CHL cases with EBV tumor status were positive. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. =. 32. years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], N=. 239; median age. =. 38. years); 22% of 346 CHL cases with EBV tumor status were positive. Results: 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. Conclusions: 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.

KW - Cytokines

KW - EBV

KW - Hodgkin lymphoma

KW - Polymorphism

KW - TNFA

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