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Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression.
Cancer Epidemiol Biomarkers Prev. 2003 Jan; 12(1):23-7.CE

Abstract

Vitamin D plays an important role in cell growth and differentiation and is proposed to protect against cancer initiation and/or progression. The vitamin D receptor (VDR) has a thymine/cytosine (T/C) polymorphism located in the first of two potential start (ATG) codons that can be detected by a RFLP using the endonuclease FokI. The C variant, which lacks the first ATG, results in a shorter VDR and is referred to as the F allele. The T variant (f allele) initiates at the first ATG. We examined the association of the VDR FokI genotype with histopathological characteristics and prognosis of prostate cancer among 191 mostly Caucasian subjects who had undergone radical prostatectomy between 1984 and 1992. The frequencies of the FF, Ff, and ff genotypes were 41%, 38%, and 21%, respectively. Subjects with the ff genotype had a lower mean percentage of Gleason grade 4/5 cancer (30.3%) than subjects with the FF or Ff genotypes (42.8% and 43.8%, respectively; P = 0.015 by t test for ff versus FF + Ff). The data suggest that the presence of an F allele increased the risk of being diagnosed with more aggressive cancer because higher percentage of Gleason grade 4/5 is associated with worse prognosis. The age-adjusted risk of prostate-specific antigen failure was lower for the ff genotype than for the FF genotype by Cox proportional hazards analysis but did not achieve statistical significance (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32). This risk reduction disappeared after further adjustment for percentage of Gleason grade 4/5, cancer volume, and preoperative serum prostate-specific antigen level (hazard ratio = 1.03; 95% confidence interval, 0.58-1.85). In conclusion, the ff genotype was associated with less aggressive histopathological findings than Ff or FF genotypes. Additional studies with a larger sample size and investigation of the functional significance of the FokI polymorphism in prostate cancer cells are warranted.

Authors+Show Affiliations

Xu Y
Department of Urology, Stanford University School of Medicine, Stanford, California 94305, USA.
Shibata A
No affiliation info available
McNeal JE
No affiliation info available
Stamey TA
No affiliation info available
Feldman D
No affiliation info available
Peehl DM
No affiliation info available

MeSH

Base SequenceCodon, InitiatorDeoxyribonucleases, Type II Site-SpecificGenotypeHumansMaleMiddle AgedPolymorphism, GeneticPrognosisProportional Hazards ModelsProstatectomyProstatic NeoplasmsReceptors, Calcitriol

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

12540499

Citation

Xu, Yue, et al. "Vitamin D Receptor Start Codon Polymorphism (FokI) and Prostate Cancer Progression." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 12, no. 1, 2003, pp. 23-7.
Xu Y, Shibata A, McNeal JE, et al. Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression. Cancer Epidemiol Biomarkers Prev. 2003;12(1):23-7.
Xu, Y., Shibata, A., McNeal, J. E., Stamey, T. A., Feldman, D., & Peehl, D. M. (2003). Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 12(1), 23-7.
Xu Y, et al. Vitamin D Receptor Start Codon Polymorphism (FokI) and Prostate Cancer Progression. Cancer Epidemiol Biomarkers Prev. 2003;12(1):23-7. PubMed PMID: 12540499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D receptor start codon polymorphism (FokI) and prostate cancer progression. AU - Xu,Yue, AU - Shibata,Atsuko, AU - McNeal,John E, AU - Stamey,Thomas A, AU - Feldman,David, AU - Peehl,Donna M, PY - 2003/1/24/pubmed PY - 2003/5/13/medline PY - 2003/1/24/entrez SP - 23 EP - 7 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol Biomarkers Prev VL - 12 IS - 1 N2 - Vitamin D plays an important role in cell growth and differentiation and is proposed to protect against cancer initiation and/or progression. The vitamin D receptor (VDR) has a thymine/cytosine (T/C) polymorphism located in the first of two potential start (ATG) codons that can be detected by a RFLP using the endonuclease FokI. The C variant, which lacks the first ATG, results in a shorter VDR and is referred to as the F allele. The T variant (f allele) initiates at the first ATG. We examined the association of the VDR FokI genotype with histopathological characteristics and prognosis of prostate cancer among 191 mostly Caucasian subjects who had undergone radical prostatectomy between 1984 and 1992. The frequencies of the FF, Ff, and ff genotypes were 41%, 38%, and 21%, respectively. Subjects with the ff genotype had a lower mean percentage of Gleason grade 4/5 cancer (30.3%) than subjects with the FF or Ff genotypes (42.8% and 43.8%, respectively; P = 0.015 by t test for ff versus FF + Ff). The data suggest that the presence of an F allele increased the risk of being diagnosed with more aggressive cancer because higher percentage of Gleason grade 4/5 is associated with worse prognosis. The age-adjusted risk of prostate-specific antigen failure was lower for the ff genotype than for the FF genotype by Cox proportional hazards analysis but did not achieve statistical significance (hazard ratio = 0.76; 95% confidence interval, 0.44-1.32). This risk reduction disappeared after further adjustment for percentage of Gleason grade 4/5, cancer volume, and preoperative serum prostate-specific antigen level (hazard ratio = 1.03; 95% confidence interval, 0.58-1.85). In conclusion, the ff genotype was associated with less aggressive histopathological findings than Ff or FF genotypes. Additional studies with a larger sample size and investigation of the functional significance of the FokI polymorphism in prostate cancer cells are warranted. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/12540499/Vitamin_D_receptor_start_codon_polymorphism__FokI__and_prostate_cancer_progression_ DB - PRIME DP - Unbound Medicine ER -