CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia

M T Tayeb, C. Clark, Neva Elizabeth Haites, Linda Sharp, Graeme Ian Murray, H.L. McLeod

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and CYP3A4 have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes have been associated with PRCa in case-control studies and may be useful to detect BPH patients that have a higher risk of developing PRCa. The association between CYP3A4 and VDR TaqI SNPs and the risk of developing PRCa have been investigated in this study by determining the variant genotype frequencies of both SNPs in 400 patients with BPH who have been followed clinically for a median of 11 years. The results of this study showed that the incidence rate of PRCa was higher in BPH patients having CYP3A4 variant genotype compared to those with wild type (relative risk (RR)=2.7; 95% CI=0.77-7.66). No association between variant genotype and risk of developing PRCa was observed with the VDR TaqI variant genotype. In addition, the results of combined genotype analysis of these two SNPs showed a borderline significant association between CYP3A4 and VDR TaqI combined variant genotypes and PRCa risk (RR=3.43; 95% CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease.
Original languageEnglish
Pages (from-to)928-932
Number of pages5
JournalBritish Journal of Cancer
Volume88
Issue number6
Early online date18 Mar 2003
DOIs
Publication statusPublished - 2003

Fingerprint

Cytochrome P-450 CYP3A
Calcitriol Receptors
Hyperplasia
Prostate
Prostatic Neoplasms
Genes
Genotype
Prostatic Hyperplasia
Single Nucleotide Polymorphism
Case-Control Studies
Cell Differentiation
Cause of Death
Cohort Studies
Cell Proliferation

Keywords

  • Case-Control Studies
  • Cell Differentiation
  • Cell Division
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System
  • Genotype
  • Humans
  • Male
  • Polymorphism, Genetic
  • Prostatic Hyperplasia
  • Prostatic Neoplasms
  • Receptors, Calcitriol
  • Risk Factors
  • CYP3A4
  • vitamin D receptor
  • prostate cancer
  • polymorphism
  • benign prostate hyperplasia
  • gene–gene interaction

Cite this

CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia. / Tayeb, M T; Clark, C.; Haites, Neva Elizabeth; Sharp, Linda; Murray, Graeme Ian; McLeod, H.L.

In: British Journal of Cancer, Vol. 88, No. 6, 2003, p. 928-932.

Research output: Contribution to journalArticle

Tayeb, M T ; Clark, C. ; Haites, Neva Elizabeth ; Sharp, Linda ; Murray, Graeme Ian ; McLeod, H.L. / CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia. In: British Journal of Cancer. 2003 ; Vol. 88, No. 6. pp. 928-932.
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abstract = "Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and CYP3A4 have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes have been associated with PRCa in case-control studies and may be useful to detect BPH patients that have a higher risk of developing PRCa. The association between CYP3A4 and VDR TaqI SNPs and the risk of developing PRCa have been investigated in this study by determining the variant genotype frequencies of both SNPs in 400 patients with BPH who have been followed clinically for a median of 11 years. The results of this study showed that the incidence rate of PRCa was higher in BPH patients having CYP3A4 variant genotype compared to those with wild type (relative risk (RR)=2.7; 95{\%} CI=0.77-7.66). No association between variant genotype and risk of developing PRCa was observed with the VDR TaqI variant genotype. In addition, the results of combined genotype analysis of these two SNPs showed a borderline significant association between CYP3A4 and VDR TaqI combined variant genotypes and PRCa risk (RR=3.43; 95{\%} CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease.",
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TY - JOUR

T1 - CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia

AU - Tayeb, M T

AU - Clark, C.

AU - Haites, Neva Elizabeth

AU - Sharp, Linda

AU - Murray, Graeme Ian

AU - McLeod, H.L.

PY - 2003

Y1 - 2003

N2 - Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and CYP3A4 have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes have been associated with PRCa in case-control studies and may be useful to detect BPH patients that have a higher risk of developing PRCa. The association between CYP3A4 and VDR TaqI SNPs and the risk of developing PRCa have been investigated in this study by determining the variant genotype frequencies of both SNPs in 400 patients with BPH who have been followed clinically for a median of 11 years. The results of this study showed that the incidence rate of PRCa was higher in BPH patients having CYP3A4 variant genotype compared to those with wild type (relative risk (RR)=2.7; 95% CI=0.77-7.66). No association between variant genotype and risk of developing PRCa was observed with the VDR TaqI variant genotype. In addition, the results of combined genotype analysis of these two SNPs showed a borderline significant association between CYP3A4 and VDR TaqI combined variant genotypes and PRCa risk (RR=3.43; 95% CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease.

AB - Prostate cancer (PRCa) is one of the most common causes of cancer death in men and determinants of PRCa risk remain largely unidentified. Benign prostatic hyperplasia (BPH) is found in the majority of ageing men and has been associated with PRCa. Many candidate genes have been suggested to be involved in PRCa, such as those that are central to cellular growth and differentiation in the prostate gland. The vitamin D receptor (VDR) and CYP3A4 have been shown to be involved in the regulation of cell proliferation and differentiation in prostate cells. Genetic variations of these genes have been associated with PRCa in case-control studies and may be useful to detect BPH patients that have a higher risk of developing PRCa. The association between CYP3A4 and VDR TaqI SNPs and the risk of developing PRCa have been investigated in this study by determining the variant genotype frequencies of both SNPs in 400 patients with BPH who have been followed clinically for a median of 11 years. The results of this study showed that the incidence rate of PRCa was higher in BPH patients having CYP3A4 variant genotype compared to those with wild type (relative risk (RR)=2.7; 95% CI=0.77-7.66). No association between variant genotype and risk of developing PRCa was observed with the VDR TaqI variant genotype. In addition, the results of combined genotype analysis of these two SNPs showed a borderline significant association between CYP3A4 and VDR TaqI combined variant genotypes and PRCa risk (RR=3.43; 95% CI=0.99-11.77). While independent confirmation is required in further studies, these results provide a potential tool to assist prediction strategies for this important disease.

KW - Case-Control Studies

KW - Cell Differentiation

KW - Cell Division

KW - Cytochrome P-450 CYP3A

KW - Cytochrome P-450 Enzyme System

KW - Genotype

KW - Humans

KW - Male

KW - Polymorphism, Genetic

KW - Prostatic Hyperplasia

KW - Prostatic Neoplasms

KW - Receptors, Calcitriol

KW - Risk Factors

KW - CYP3A4

KW - vitamin D receptor

KW - prostate cancer

KW - polymorphism

KW - benign prostate hyperplasia

KW - gene–gene interaction

U2 - 10.1038/sj.bjc.6600825

DO - 10.1038/sj.bjc.6600825

M3 - Article

VL - 88

SP - 928

EP - 932

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 6

ER -