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

详细信息    查看全文

• 作者：Herv¨¦ Ghesqui¨¨res ; Matthew J. Maurer ; Olivier Casasnovas ; Stephen M. Ansell ; Beth R. Larrabee ; Eva Lech-Mar ; a ; 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 ; Brian K. Link ; Aspasia Stamatoullas ; Christophe Ferm¨¦ ; Ahmet Dogan ; et al.
• 关键词：Hodgkin lymphoma ; Cytokines ; Polymorphism ; TNFA ; EBV
• 刊名：Cytokine
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：64
• 期：2
• 页码：523-531
• 全文大小：453 K

文摘

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 m>IL10m> (rs1800890, rs1800896, rs1800871, rs1800872), m>TNFAm> (rs1800629), m>IL6m> (rs1800795), m>ILRNm> (rs419598), m>INFGm> (rs2430561) and m>CCL17m> (rs223828) were associated with circulating levels of related cytokines at diagnosis and progression-free survival (PFS) in CHL. Patients were from France (GELA, m>N m>= 464; median age = 32 years) and the United States (Iowa/Mayo Specialized Program Of Research Excellence [SPORE], m>N m>= 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, m>TNFAm> rs1800629 (HR_AA/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 (HR_AA/AG = 1.63; 95 % CI, 0.61-4.40). In a meta-analysis of the two studies, m>TNFAm> (HR_AA/AG = 2.11; 95 % CI, 1.18-3.77; m>P m>= 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 m>TNFAm> 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.