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MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis
A. Benner, L. Mansouri, D. Rossi, A. Majid, K. Willander, A. Parker, G. Bond, S. Pavlova, H. Nückel, O. Merkel, P. Ghia, E. Montserrat, MA. Kaderi, R. Rosenquist, G. Gaidano, MJ. Dyer, P. Söderkvist, M. Linderholm, D. Oscier, Z. Tvaruzkova, S....
Jazyk angličtina Země Itálie
Typ dokumentu časopisecké články, metaanalýza
NLK
Directory of Open Access Journals
od 1994
Free Medical Journals
od 1994
Freely Accessible Science Journals
od 1994
PubMed Central
od 2009
Europe PubMed Central
od 2009
Open Access Digital Library
od 1994-01-01
ROAD: Directory of Open Access Scholarly Resources
od 1996
- MeSH
- chronická lymfatická leukemie diagnóza genetika MeSH
- databáze faktografické * trendy MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- promotorové oblasti (genetika) genetika MeSH
- protoonkogenní proteiny c-mdm2 genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
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.
Department of Cancer Studies and Molecular Medicine MRC Toxicology Unit University of Leicester UK
Department of Clinical and Experimental Medicine Linköping University Sweden
Department of Hematology Royal Bournemouth Hospital UK
Department of Hematology University Hospital University of Duisburg Essen Essen Germany
Department of Internal Medicine 3 University of Ulm Germany
Division of Biostatistics German Cancer Research Center Heidelberg Germany
Ludwig Institute for Cancer Research University of Oxford UK
Citace poskytuje Crossref.org
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- $a 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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