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Allelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer risk.
Modugno, F; Weissfeld, J L; Trump, D L; Zmuda, J M; Shea, P; Cauley, J A; Ferrell, R E.
Affiliation
  • Modugno F; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. fm@cs.cmu.edu
Clin Cancer Res ; 7(10): 3092-6, 2001 Oct.
Article in En | MEDLINE | ID: mdl-11595700
PURPOSE: The purpose of this study was to determine whether polymorphisms in the CAG repeat in exon 1 of the androgen receptor (AR), two intronic restriction sites in the estrogen receptor (ESR1 XbaI and ESR1 PvuII), and an Arg264Cy5 substitution in the aromatase gene (CYP19) contribute to prostate cancer risk. EXPERIMENTAL DESIGN: A case-control study was performed with 88 Caucasian prostate cancer patients and 241 Caucasian male controls. Logistic regression models were used to assess individual and joint contributions of genotypes to prostate cancer risk. RESULTS: For single polymorphisms, only the AR repeat number was significantly related to increased prostate cancer risk [age- and body mass index (BMI)-adjusted odds ratio (OR), 1.14; 95% confidence interval (CI), 1.04-1.25], suggesting a 14% increase in risk for each missing CAG repeat. When subjects were classified as either long (> or =23 AR CAG repeats) or short (<23 repeats) carriers, a significant increase in risk was also observed (age- and BMI-adjusted OR, 1.75; 95% CI, 1.05-2.95; P = 0.04). The aromatase C/T was associated with an increase in risk of borderline significance (age- and BMI-adjusted OR, 2.50; 95% CI, 0.99-6.28). When examining the effects of two polymorphisms on prostate cancer risk, homozygosity for the ESR1 XbaI restriction site together with a longer AR was more frequent among controls (32%) than cases (18%; age- and BMI-adjusted OR, 0.39; 95% CI, 0.19-0.78). The aromatase C/C genotype together with a longer AR was also more frequent among controls (55%) than cases (41%; age- and BMI-adjusted OR, 0.51; 95% CI, 0.30-0.89). CONCLUSIONS: Estrogen and aromatase may play a role in prostate cancer. A multigenic model of prostate cancer susceptibility is also supported.
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Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Aromatase / Receptors, Androgen / Receptors, Estrogen / Trinucleotide Repeats Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Humans / Male Language: En Journal: Clin Cancer Res Journal subject: NEOPLASIAS Year: 2001 Document type: Article Affiliation country: United States Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Prostatic Neoplasms / Aromatase / Receptors, Androgen / Receptors, Estrogen / Trinucleotide Repeats Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Humans / Male Language: En Journal: Clin Cancer Res Journal subject: NEOPLASIAS Year: 2001 Document type: Article Affiliation country: United States Country of publication: United States