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@ARTICLE{Benner:119640,
author = {A. Benner$^*$ and L. Mansouri and D. Rossi and A. Majid and
K. Willander and A. Parker and G. Bond and S. Pavlova and H.
Nückel and O. Merkel and P. Ghia and E. Montserrat and M.
A. Kaderi and R. Rosenquist and G. Gaidano and M. J. S. Dyer
and P. Söderkvist and M. Linderholm and D. Oscier and Z.
Tvaruzkova and S. Pospisilova and U. Dührsen and R. Greil
and H. Döhner and S. Stilgenbauer and T. Zenz$^*$},
collaboration = {E. R. I. o. CLL},
title = {{MDM}2 promotor polymorphism and disease characteristics in
chronic lymphocytic leukemia: results of an individual
patient data-based meta-analysis.},
journal = {Haematologica},
volume = {99},
number = {8},
issn = {1592-8721},
address = {Pavia},
publisher = {Ferrata Storti Foundation},
reportid = {DKFZ-2017-00271},
pages = {1285 - 1291},
year = {2014},
abstract = {A number of single nucleotide polymorphisms have been
associated with disease predisposition in chronic
lymphocytic leukemia. A single nucleotide polymorphism in
the MDM2 promotor region, MDM2SNP309, was shown to soothe
the p53 pathway. In the current study, we aimed to clarify
the effect of the MDM2SNP309 on chronic lymphocytic leukemia
characteristics and outcome. We performed a meta-analysis of
data from 2598 individual patients from 10 different
cohorts. Patients' data and genetic analysis for MDM2SNP309
genotype, immunoglobulin heavy chain variable region
mutation status and fluorescence in situ hybridization
results were collected. There were no differences in overall
survival based on the polymorphism (log rank test,
stratified by study cohort; P=0.76; GG genotype:
cohort-adjusted median overall survival of 151 months; TG:
153 months; TT: 149 months). In a multivariable Cox
proportional hazards regression analysis, advanced age, male
sex and unmutated immunoglobulin heavy chain variable region
genes were associated with inferior survival, but not the
MDM2 genotype. The MDM2SNP309 is unlikely to influence
disease characteristics and prognosis in chronic lymphocytic
leukemia. Studies investigating the impact of individual
single nucleotide polymorphisms on prognosis are often
controversial. This may be due to selection bias and small
sample size. A meta-analysis based on individual patient
data provides a reasonable strategy for prognostic factor
analyses in the case of small individual studies. Individual
patient data-based meta-analysis can, therefore, be a
powerful tool to assess genetic risk factors in the absence
of large studies.},
keywords = {MDM2 protein, human (NLM Chemicals) / Proto-Oncogene
Proteins c-mdm2 (NLM Chemicals)},
cin = {C060 / G100},
ddc = {610},
cid = {I:(DE-He78)C060-20160331 / I:(DE-He78)G100-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25082786},
pmc = {pmc:PMC4116826},
doi = {10.3324/haematol.2013.101170},
url = {https://inrepo02.dkfz.de/record/119640},
}