© 1997 by Oxford University Press
Journal Of The National Cancer Institute, Vol 89, 166-170, Copyright © 1997 by Oxford University Press
SA Ingles, RK Ross, MC Yu, RA Irvine, G La Pera, RW Haile and GA Coetzee
BACKGROUND: Prostate cancer is an increasingly common disease for which
there are few well-established risk factors. Family history data suggest a
genetic component; however, the majority of prostate cancer cases cannot be
explained by a single-gene model. Prostate cell division is influenced by
two steroid hormones, testosterone and vitamin D, the action of each being
mediated by its respective receptor. The genes for the two receptors are
candidates in a multigenic model for prostate cancer susceptibility.
PURPOSE: We examined genetic polymorphisms in two steroid receptors, the
androgen receptor (AR) and the vitamin D receptor (VDR), in a case-control
pilot study of prostate cancer. METHODS: Fifty-seven non-Hispanic white
case patients with prostate cancer and 169 non-Hispanic white control
subjects were genotyped for a previously described microsatellite (CAG
repeats) in the AR gene and for a newly discovered poly-A microsatellite in
the 3'-untranslated region (3'UTR) of the VDR gene. To compare genotypes
with respect to prostate cancer risk, we estimated odds ratios (ORs) by
using logistic regression. ORs were also estimated separately for advanced
and localized cases of disease. All P values resulted from two-sided tests.
RESULTS: Both the AR and the VDR polymorphisms were associated,
individually and after mutual adjustment, with prostate cancer. Adjusted
ORs (95% confidence intervals [CIs]) for prostate cancer were 2.10 (95% CI
= 1.11-3.99) for individuals carrying an AR CAG allele with fewer than 20
repeats versus an allele with 20 or more repeats and 4.61 (95% CI =
1.34-15.82) for individuals carrying at least one long (A18 to A22) VDR
poly-A allele versus two short (A14 to A17) poly-A alleles. For both the AR
and VDR genes, the at-risk genotypes were more strongly associated with
advanced disease than with localized disease. CONCLUSIONS: In this pilot
study, genetic variation in both the VDR and the AR genes was associated
with prostate cancer, and both genes appear to preferentially confer risk
for advanced disease. These two genetic risk factors, if confirmed, are
among the strongest risk factors yet identified for prostate cancer.
IMPLICATIONS: These results are consistent with a multigenic model of
prostate cancer susceptibility. On the basis of the joint effect of several
genetic loci, one might ultimately be able to construct a risk profile to
predict advanced disease, so that men whose disease is unlikely to progress
to an advanced stage can possibly be spared aggressive treatment.
ARTICLES
Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor
Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033- 0800, USA.
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A. B. Spurdle, G. S. Dite, X. Chen, C. J. Mayne, M. C. Southey, L. E. Batten, H. Chy, L. Trute, M. R. E. McCredie, G. G. Giles, et al. Androgen Receptor Exon 1 CAG Repeat Length and Breast Cancer in Women Before Age Forty Years J Natl Cancer Inst, June 2, 1999; 91(11): 961 - 966. [Abstract] [Full Text] [PDF]
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D. C. Smith, C. S. Johnson, C. C. Freeman, J. Muindi, J. W. Wilson, and D. L. Trump A Phase I Trial of Calcitriol (1,25-Dihydroxycholecalciferol) in Patients with Advanced Malignancy Clin. Cancer Res., June 1, 1999; 5(6): 1339 - 1345. [Abstract] [Full Text] [PDF]
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P. J. Malloy, J. W. Pike, and D. Feldman The Vitamin D Receptor and the Syndrome of Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets Endocr. Rev., April 1, 1999; 20(2): 156 - 188. [Abstract] [Full Text]
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L. N. Kolonel, A. M. Y. Nomura, and R. V. Cooney Dietary Fat and Prostate Cancer: Current Status J Natl Cancer Inst, March 3, 1999; 91(5): 414 - 428. [Abstract] [Full Text] [PDF]
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B. L. Lokeshwar, G. G. Schwartz, M. G. Selzer, K. L. Burnstein, S.-H. Zhuang, N. L. Block, and L. Binderup Inhibition of Prostate Cancer Metastasis in Vivo: A Comparison of 1,25-Dihydroxyvitamin D (Calcitriol) and EB1089 Cancer Epidemiol. Biomarkers Prev., March 1, 1999; 8(3): 241 - 248. [Abstract] [Full Text] [PDF]
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E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken Molecular Genetics and Epidemiology of Prostate Carcinoma Endocr. Rev., February 1, 1999; 20(1): 22 - 45. [Abstract] [Full Text]
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J. R. Cerhan, A. S. Parker, S. D. Putnam, B. C-H. Chiu, C. F. Lynch, M. B. Cohen, J. C. Torner, and K. P. Cantor Family History and Prostate Cancer Risk in a Population-Based Cohort of Iowa Men Cancer Epidemiol. Biomarkers Prev., January 1, 1999; 8(1): 53 - 60. [Abstract] [Full Text]
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C. Lopez-Otin and E. P. Diamandis Breast and Prostate Cancer: An Analysis of Common Epidemiological, Genetic, and Biochemical Features Endocr. Rev., August 1, 1998; 19(4): 365 - 396. [Abstract] [Full Text] [PDF]
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