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The CAG Repeat within the Androgen Receptor Gene and its Relationship to Prostate Cancer

The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether sh...

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Published in:Proceedings of the National Academy of Sciences - PNAS 1997-04, Vol.94 (7), p.3320-3323
Main Authors: Giovannucci, Edward, Stampfer, Meir J., Krithivas, Krishna, Brown, Myles, Brufsky, Adam, Talcott, James, Hennekens, Charles H., Kantoff, Philip W.
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cited_by cdi_FETCH-LOGICAL-c579t-225a632751671e36a21b40abc31a0f5c9909235497be9f1378573e8997cd0a9c3
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container_title Proceedings of the National Academy of Sciences - PNAS
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creator Giovannucci, Edward
Stampfer, Meir J.
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Kantoff, Philip W.
description The length of a polymorphic CAG repeat sequence, occurring in the androgen receptor gene, is inversely correlated with transcriptional activity by the androgen receptor. Because heightened androgenic stimulation may increase risk of prostate cancer development and progression, we examined whether shorter CAG repeats in the androgen receptor gene are related to higher risk of prostate cancer. We conducted a nested case-control study of 587 newly diagnosed cases of prostate cancer detected between 1982 and 1995, and 588 controls without prostate cancer, within the Physician's Health Study. An association existed between fewer androgen receptor gene CAG repeats and higher risk of total prostate cancer [relative risk (RR) = 1.52; 95% confidence interval (CI) = 0.92-2.49; P trend = 0.04; for men with CAG repeat lengths ≤ 18 relative to ≥ 26 repeats]. In particular, a shorter CAG repeat sequence was associated with cancers characterized by extraprostatic extension or distant metastases (stage C or D) or high histologic grade (RR = 2.14; CI = 1.14-4.01; P trend = 0.001). This association was observed individually both for high stage (RR = 2.23) and high grade prostate cancer (RR = 1.89). Men with shorter repeats were at particularly high risk for distant metastatic and fatal prostate cancer. Variability in the CAG repeat length was not associated with low grade or low stage disease. These results demonstrate that a shorter CAG repeat sequence in the androgen receptor gene predicts higher grade and advanced stage of prostate cancer at diagnosis, and metastasis and mortality from the disease. The clinical implications of these results should be evaluated further.
doi_str_mv 10.1073/pnas.94.7.3320
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source JSTOR Archival Journals and Primary Sources Collection; PubMed Central
subjects Adult
Aged
Aged, 80 and over
Androgen receptors
Androgens
Biological Sciences
Blood
Cancer
Case-Control Studies
Disease risk
Genes
Humans
Logistic regression
Male
Medical research
Middle Aged
Mortality
Polymorphism, Genetic
Prostate
Prostate cancer
Prostatic diseases
Prostatic Neoplasms - genetics
Receptors, Androgen - genetics
Trinucleotide Repeats
title The CAG Repeat within the Androgen Receptor Gene and its Relationship to Prostate Cancer
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