TY - JOUR
T1 - MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia
T2 - Results of an individual patient data-based meta-analysis
AU - Benner, Axel
AU - Mansouri, Larry
AU - Rossi, Davide
AU - Majid, Aneela
AU - Willander, Kerstin
AU - Parker, Anton
AU - Bond, Gareth
AU - Pavlova, Sarka
AU - Nückel, Holger
AU - Merkel, Olaf
AU - Ghia, Paolo
AU - Montserrat, Emili
AU - Kaderi, Mohd Arifin
AU - Rosenquist, Richard
AU - Gaidano, Gianluca
AU - Dyer, Martin J.S.
AU - Söderkvist, Peter
AU - Linderholm, Mats
AU - Oscier, David
AU - Tvaruzkova, Zuzana
AU - Pospisilova, Sarka
AU - Dührsen, Ulrich
AU - Greil, Richard
AU - Döhner, Hartmut
AU - Stilgenbauer, Stephan
AU - Zenz, Thorsten
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84905163701&partnerID=8YFLogxK
U2 - 10.3324/haematol.2013.101170
DO - 10.3324/haematol.2013.101170
M3 - Article
SN - 0390-6078
VL - 99
SP - 1285
EP - 1291
JO - Haematologica
JF - Haematologica
IS - 8
ER -