Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukaemia once treatment is initiated

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Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukaemia once treatment is initiated. / Starczynski, J; Pepper, C; Pratt, Guy; Hooper, L; Thomas, A; Milligan, Donald; Bentley, P; Fegan, Christopher.

In: Journal of Clinical Oncology, Vol. 23, 31.01.2005, p. 1514-1521.

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@article{238d3c9bb189410a9e5168d0e5275fc3,
title = "Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukaemia once treatment is initiated",
abstract = "Purpose Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance, The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia. Patients and Methods The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome. Results The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed. Conclusion The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.",
author = "J Starczynski and C Pepper and Guy Pratt and L Hooper and A Thomas and Donald Milligan and P Bentley and Christopher Fegan",
year = "2005",
month = jan,
day = "31",
doi = "10.1200/JCO.2005.02.192",
language = "English",
volume = "23",
pages = "1514--1521",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",

}

RIS

TY - JOUR

T1 - Common polymorphism G(-248)A in the promoter region of the bax gene results in significantly shorter survival in patients with chronic lymphocytic leukaemia once treatment is initiated

AU - Starczynski, J

AU - Pepper, C

AU - Pratt, Guy

AU - Hooper, L

AU - Thomas, A

AU - Milligan, Donald

AU - Bentley, P

AU - Fegan, Christopher

PY - 2005/1/31

Y1 - 2005/1/31

N2 - Purpose Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance, The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia. Patients and Methods The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome. Results The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed. Conclusion The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.

AB - Purpose Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance, The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia. Patients and Methods The frequency of the novel polymorphism, G(-248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome. Results The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed. Conclusion The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.

UR - http://www.scopus.com/inward/record.url?scp=14944346868&partnerID=8YFLogxK

U2 - 10.1200/JCO.2005.02.192

DO - 10.1200/JCO.2005.02.192

M3 - Article

C2 - 15735127

VL - 23

SP - 1514

EP - 1521

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

ER -