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MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis

Benner, Axel and Mansouri, Larry and Rossi, Davide and Majid, Aneela and Willander, Kerstin and Parker, Anton and Bond, Gareth and Pavlova, Sarka and Nückel, Holger and Merkel, Olaf and Ghia, Paolo and Montserrat, Emili and Kaderi, Mohd Arifin and Rosenquist, Richard and Gaidano, Gianluca and Dye, Martin J.S. and Söderkvist, Peter and Linderholm, Mats and Oscier, David and Tvaruzkova, Zuzana and Pospisilova, Sarka and Dührse, Ulrich and Greil, Richard and Döhner, Hartmut and Stilgenbauer, Stephan and Zenz, Thorsten (2014) MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis. Haematologica, 99 (8). pp. 1285-1291. ISSN 1592-8721

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Abstract

A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lympho- cytic 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 lym- phocytic 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 dif- ferences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG geno- type: 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 selec- tion 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.

Item Type: Article (Journal)
Additional Information: 4643/38695
Uncontrolled Keywords: MDM2 promotor polymorphism, chronic lymphocytic leukemia, data-based meta-analysis
Subjects: Q Science > Q Science (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Kulliyyahs/Centres/Divisions/Institutes: Kulliyyah of Allied Health Sciences > Department of Basic Health Sciences (Until June 2011)
Depositing User: Dr Mohd. Arifin Bin Kaderi
Date Deposited: 10 Oct 2014 16:27
Last Modified: 21 Sep 2017 10:12
URI: http://irep.iium.edu.my/id/eprint/38695

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