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000119640 0247_ $$2doi$$a10.3324/haematol.2013.101170
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000119640 0247_ $$2ISSN$$a1592-8721
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000119640 1001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b0$$eFirst author$$udkfz
000119640 245__ $$aMDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis.
000119640 260__ $$aPavia$$bFerrata Storti Foundation$$c2014
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000119640 520__ $$aA 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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000119640 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aMDM2 protein, human
000119640 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aProto-Oncogene Proteins c-mdm2
000119640 7001_ $$aMansouri, Larry$$b1
000119640 7001_ $$aRossi, Davide$$b2
000119640 7001_ $$aMajid, Aneela$$b3
000119640 7001_ $$aWillander, Kerstin$$b4
000119640 7001_ $$aParker, Anton$$b5
000119640 7001_ $$aBond, Gareth$$b6
000119640 7001_ $$aPavlova, Sarka$$b7
000119640 7001_ $$aNückel, Holger$$b8
000119640 7001_ $$aMerkel, Olaf$$b9
000119640 7001_ $$aGhia, Paolo$$b10
000119640 7001_ $$aMontserrat, Emili$$b11
000119640 7001_ $$aKaderi, Mohd Arifin$$b12
000119640 7001_ $$aRosenquist, Richard$$b13
000119640 7001_ $$aGaidano, Gianluca$$b14
000119640 7001_ $$aDyer, Martin J S$$b15
000119640 7001_ $$aSöderkvist, Peter$$b16
000119640 7001_ $$aLinderholm, Mats$$b17
000119640 7001_ $$aOscier, David$$b18
000119640 7001_ $$aTvaruzkova, Zuzana$$b19
000119640 7001_ $$aPospisilova, Sarka$$b20
000119640 7001_ $$aDührsen, Ulrich$$b21
000119640 7001_ $$aGreil, Richard$$b22
000119640 7001_ $$aDöhner, Hartmut$$b23
000119640 7001_ $$aStilgenbauer, Stephan$$b24
000119640 7001_ $$0P:(DE-He78)f3d5f16b49eb47520def635be98d5576$$aZenz, Thorsten$$b25$$udkfz
000119640 7001_ $$aCLL, European Research Initiative on$$b26$$eCollaboration Author
000119640 773__ $$0PERI:(DE-600)2805244-4$$a10.3324/haematol.2013.101170$$gVol. 99, no. 8, p. 1285 - 1291$$n8$$p1285 - 1291$$tHaematologica$$v99$$x1592-8721$$y2014
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