The CYP2D6 extensive metabolizer genotype is associated with increased risk for bladder cancer

Sherif Abdel-Rahman, Wagida A. Anwar, Wafaa E. Abdel-Aal, Magdy A. Ghoneim, William W. Au

Research output: Contribution to journalArticle

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Abstract

Inheritance of certain polymorphic metabolizing genes is associated with the development of a number of environmental cancers and may also influence the clinicopathological tumor outcome. We have investigated the association between the inheritance of the polymorphic cytochrome P-450 2D6 (CYP2D6) gene and the development of transitional and squamous cell carcinomas (TCC and SCC) of the bladder in 37 Egyptian cancer patients and 27 matched controls. Genotypic analysis using the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) assays revealed that the CYP2D6 extensive metabolizer genotype (CYP2D6*1A) is over represented in bladder cancer patients compared to controls (79 versus 44%, respectively) and is significantly associated with increased risk for bladder cancer (odds ratio (OR) = 4.5, 95% confidence limit (CL) = 1.3-15.7, P = 0.006). Our results also indicate that individuals who have inherited this genotype are more likely to develop TCC (OR = 5.9, 95% CL = 1.4-27.9, P = 0.006) rather than SCC (OR = 3.1, 95% CL = 0.7-15.9; P = 0.09). When the relative risk associated with this genotype was estimated among subjects who were smokers or schistosoma infected, the same tendency towards the development of TCC was observed. These data suggest that the predisposing CYP2D6 gene may not only increase the risk for bladder cancer among Egyptians, but may also influence the clinicopathological tumor outcome.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalCancer Letters
Volume119
Issue number1
DOIs
StatePublished - Oct 28 1997

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Urinary Bladder Neoplasms
Cytochrome P-450 Enzyme System
Genotype
Odds Ratio
Neoplasms
Genes
Schistosoma
Transitional Cell Carcinoma
Restriction Fragment Length Polymorphisms
Squamous Cell Carcinoma
Urinary Bladder
Polymerase Chain Reaction

Keywords

  • Bilharzia
  • Bladder cancer
  • CYP2D6
  • Cytochrome P-450 schistosoma
  • Genetic polymorphism
  • Genetic susceptibility
  • PCR
  • RFLP

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

The CYP2D6 extensive metabolizer genotype is associated with increased risk for bladder cancer. / Abdel-Rahman, Sherif; Anwar, Wagida A.; Abdel-Aal, Wafaa E.; Ghoneim, Magdy A.; Au, William W.

In: Cancer Letters, Vol. 119, No. 1, 28.10.1997, p. 115-122.

Research output: Contribution to journalArticle

Abdel-Rahman, Sherif ; Anwar, Wagida A. ; Abdel-Aal, Wafaa E. ; Ghoneim, Magdy A. ; Au, William W. / The CYP2D6 extensive metabolizer genotype is associated with increased risk for bladder cancer. In: Cancer Letters. 1997 ; Vol. 119, No. 1. pp. 115-122.
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abstract = "Inheritance of certain polymorphic metabolizing genes is associated with the development of a number of environmental cancers and may also influence the clinicopathological tumor outcome. We have investigated the association between the inheritance of the polymorphic cytochrome P-450 2D6 (CYP2D6) gene and the development of transitional and squamous cell carcinomas (TCC and SCC) of the bladder in 37 Egyptian cancer patients and 27 matched controls. Genotypic analysis using the polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) assays revealed that the CYP2D6 extensive metabolizer genotype (CYP2D6*1A) is over represented in bladder cancer patients compared to controls (79 versus 44{\%}, respectively) and is significantly associated with increased risk for bladder cancer (odds ratio (OR) = 4.5, 95{\%} confidence limit (CL) = 1.3-15.7, P = 0.006). Our results also indicate that individuals who have inherited this genotype are more likely to develop TCC (OR = 5.9, 95{\%} CL = 1.4-27.9, P = 0.006) rather than SCC (OR = 3.1, 95{\%} CL = 0.7-15.9; P = 0.09). When the relative risk associated with this genotype was estimated among subjects who were smokers or schistosoma infected, the same tendency towards the development of TCC was observed. These data suggest that the predisposing CYP2D6 gene may not only increase the risk for bladder cancer among Egyptians, but may also influence the clinicopathological tumor outcome.",
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