title: The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.
abstract: The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Skogsberg
authors.forename: G
authors.initials: G
authors.lastname: Tobin
authors.forename: A
authors.initials: A
authors.lastname: Kröber
authors.forename: D
authors.initials: D
authors.lastname: Kienle
authors.forename: U
authors.initials: U
authors.lastname: Thunberg
authors.forename: A
authors.initials: A
authors.lastname: Aleskog
authors.forename: K
authors.initials: K
authors.lastname: Karlsson
authors.forename: A
authors.initials: A
authors.lastname: Laurell
authors.forename: M
authors.initials: M
authors.lastname: Merup
authors.forename: J
authors.initials: J
authors.lastname: Vilpo
authors.forename: C
authors.initials: C
authors.lastname: Sundström
authors.forename: G
authors.initials: G
authors.lastname: Roos
authors.forename: H
authors.initials: H
authors.lastname: Jernberg-Wiklund
authors.forename: H
authors.initials: H
authors.lastname: Döhner
authors.forename: K
authors.initials: K
authors.lastname: Nilsson
authors.forename: S
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: R
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D015996:Survival Rate; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D051028:bcl-2-Associated X Protein