Analyse von Interleukin-10-Genvariationen bei diffus großzelligen B-Zell-Lymphomen

Analyse von Interleukin-10-Genvariationen bei diffus großzelligen B-Zell-Lymphomen

Analysis of Interleukin-10 gene variations in diffuse large B-cell lymphoma

Julia Stächele

Doctoral thesis

Date of Examination: 2016-09-22

Date of issue: 2016-09-12

Advisor: Kube, Dieter Prof. Dr.

Referee: Kube, Dieter Prof. Dr.

Referee: Beißbarth, Tim Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0028-882F-6

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Abstract

English

Although Non-Hodgkin lymphoma principally can be cured due to current therapy strategies some patients do not achieve complete remission. Besides many patients are affected by significant therapy-related toxicities. In searching for new clinically relevant and applicable prognostic markers gene variations in cytokines are increasingly taken into consideration since they may be involved in the development and clinical course of lymphomas. Therefore we analyzed three distal single nucleotide polymorphisms (IL-10-12.806TC, IL-10-11.777GA und IL-10-11.668GA) as well as one gene variation of the 3’UTR of the Interleukin-10 (IL-10) gene (IL-10+4.259AG) in 594 patients with diffuse large B-cell lymphoma (DLBCL). Furthermore the IL-10 gene expression has been studied since particular IL-10 gene variations may be associated with distinct IL-10 expression. Within genotyping analyses the already established SNaPshot analysis could be successfully extended to a multiplex assay. Apart from univariate analyses of the gene variations we also performed multivariate analyses adjusted to IPI factos. Hereby no significant differences concerning overall survival and event-free survival could be found. Nevertheless DLBCL patients carrying genotype AA of the gene variation IL-10-11.777GA tend to show better event-free survival in contrast to heterozygote carriers. In addition, genotype AA of the gene variation IL-10+4.259AG may be associated with the development of a DLBCL since this genotype was significantly more frequent among patients compared with healthy controls. Since there was only partially evidence for interindividual differences in IL-10 gene expression further studies should be conducted.

Keywords: Interleukin-10; gene variations; diffuse large B-cell lymphoma