BENNER, A., L. MANSOURI, D. ROSSI, A. MAJID, K. WILLANDER, A. PARKER, G. BOND, Šárka PAVLOVÁ, H. NUCKEL, O. MERKEL, P. GHIA, E. MONTSERRAT, MA KADERI, R. ROSENQUIST, G. GAIDANO, MJ. DYER, P. SODERKVIST, M. LINDERHOLM, D. OSCIER, Zuzana TVARŮŽKOVÁ, Šárka POSPÍŠILOVÁ, U. DUHRSEN, R. GREIL, H. DOHNER, S. STILGENBAUER and T. ZENZ. MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis. Haematologica/the hematology journal. Itálie: Fondazione Ferrata Storti, 2014, vol. 99, No 8, p. 1285-1291. ISSN 0390-6078. doi:10.3324/haematol.2013.101170.
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Basic information
Original name MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis
Authors BENNER, A. (276 Germany), L. MANSOURI (752 Sweden), D. ROSSI (380 Italy), A. MAJID (826 United Kingdom of Great Britain and Northern Ireland), K. WILLANDER (826 United Kingdom of Great Britain and Northern Ireland), A. PARKER (826 United Kingdom of Great Britain and Northern Ireland), G. BOND (826 United Kingdom of Great Britain and Northern Ireland), Šárka PAVLOVÁ (203 Czech Republic, belonging to the institution), H. NUCKEL (276 Germany), O. MERKEL (40 Austria), P. GHIA (380 Italy), E. MONTSERRAT (724 Spain), MA KADERI (752 Sweden), R. ROSENQUIST (752 Sweden), G. GAIDANO (380 Italy), MJ. DYER (826 United Kingdom of Great Britain and Northern Ireland), P. SODERKVIST (752 Sweden), M. LINDERHOLM (752 Sweden), D. OSCIER (826 United Kingdom of Great Britain and Northern Ireland), Zuzana TVARŮŽKOVÁ (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), U. DUHRSEN (276 Germany), R. GREIL (40 Austria), H. DOHNER (276 Germany), S. STILGENBAUER (276 Germany) and T. ZENZ (276 Germany).
Edition Haematologica/the hematology journal, Itálie, Fondazione Ferrata Storti, 2014, 0390-6078.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher Italy
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 5.814
RIV identification code RIV/00216224:14740/14:00078337
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.3324/haematol.2013.101170
UT WoS 000342834300011
Keywords in English MDM2; data-based; meta-analysis; CLL; promotor; polymorphism
Tags kontrola MP, rivok
Tags International impact, Reviewed
Changed by Changed by: Martina Prášilová, učo 342282. Changed: 25/2/2015 13:37.
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.
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