title: BCL2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia.
abstract: A number of single nucleotide polymorphisms (SNP) have been implicated to impact upon the disease course of chronic lymphocytic leukemia (CLL). However, few of these association studies could be confirmed in independent studies in the past. Recently, three independent studies did not confirm the prognostic impact of a new functional SNP in the BCL2 gene (-938C>A) described by Nückel et al. For this reason we genotyped an independent group of patients with CLL (n = 271) with mature follow up and detailed analysis of molecular genetics. The genotype distribution of this BCL2 polymorphism did not differ from that described in the original work. However, genotypes were not associated with time to first treatment (TFT) and overall survival (OS) in univariate or multivariate analysis in the current cohort. Comparing the characteristics of the two study cohorts in more detail we found differences between the two cohorts demonstrating a potentially more aggressive second study cohort. However, TFT and OS in patients with CLL according to Binet A did not differ significantly depending on the genotype. Our findings underscore the need for optimally matched patient cohorts in replication studies. The study re-emphasizes the need for large cohorts and validation in independent data sets before firm conclusions can be made about genotype-phenotype associations.
authors.affiliation: Department of Hematology and Oncology, University Ulm, Ulm, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
mesh_terms: D015331:Cohort Studies; D018450:Disease Progression; D005787:Gene Frequency; D005838:Genotype; D005858:Germany; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015810:Linkage Disequilibrium; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2