Universität zu Köln

Linnebank, M., Moskau, S., Kowoll, A., Semmler, A., Bangard, C., Vogt-Schaden, M., Egerer, G., Schackert, G., Reichmann, H., Schmidt-Wolf, I. G. H., Pels, H. and Schlegel, U. (2012). Association of transcobalamin c. 776C > G with overall survival in patients with primary central nervous system lymphoma. Br. J. Cancer, 107 (11). S. 1840 - 1844. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827

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Abstract

BACKGROUND: Chemotherapy for primary central nervous system lymphoma (PCNSL) is based on methotrexate (MTX), which interferes with both nucleic acid synthesis and methionine metabolism. We have reported previously that genetic variants with influence on methionine metabolism are associated with MTX side effects, that is, the occurrence of white matter lesions as a sign of MTX neurotoxicity. Here, we investigated whether such variants are associated with MTX efficacy in terms of overall survival in MTX-treated PCNSL patients. METHODS: We analysed seven genetic variants influencing methionine metabolism in 68 PCNSL patients treated with systemic and facultative intraventricular MTX-based polychemotherapy (Bonn protocol). RESULTS: Median age at diagnosis was 59 years (range: 28-77), 32 patients were female. Younger age (Wald = 8.9; P = 0.003) and the wild-type C (CC) allele of the genotype transcobalamin c (Tc2). 776C>G (Wald = 6.7; P = 0.010) were associated with longer overall survival in a multivariate COX regression analysis. CONCLUSION: This observation suggests that the missense variant Tc2. 776C>G influences both neurotoxicity and efficacy of MTX in the Bonn PCNSL protocol. British Journal of Cancer (2012) 107, 1840-1843. doi:10.1038/bjc.2012.476 www.bjcancer.com Published online 25 October 2012 (C) 2012 Cancer Research UK

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Linnebank, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moskau, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kowoll, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Semmler, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bangard, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogt-Schaden, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Egerer, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schackert, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reichmann, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Wolf, I. G. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pels, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlegel, U. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-478551
DOI:	10.1038/bjc.2012.476
Journal or Publication Title:	Br. J. Cancer
Volume:	107
Number:	11
Page Range:	S. 1840 - 1844
Date:	2012
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1532-1827
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WHITE-MATTER CHANGES; METHIONINE METABOLISM; CHEMOTHERAPY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47855