TY - JOUR
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 M.
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 M.
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
N1 - Funding Information:
This work was supported by a grant from the French Ministry of Health (PHRC 1998 and 2002); la Fondation de France (postdoctoral fellowship, H.G.); Philippe Foundation (postdoctoral fellowship, H.G.); Grants CA92104, CA92153, CA97274, and CA25224 from the US National Institutes of Health; and by the Predolin Foundation.
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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U2 - 10.1016/j.cyto.2013.08.002
DO - 10.1016/j.cyto.2013.08.002
M3 - Article
C2 - 24008079
AN - SCOPUS:84885189071
SN - 1043-4666
VL - 64
SP - 523
EP - 531
JO - Cytokine
JF - Cytokine
IS - 2
ER -