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The CAG repeat within the androgen receptor gene and its relationship to prostate cancer.
Proc Natl Acad Sci U S A. 1997 Apr 01; 94(7):3320-3.PN

Abstract

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 < or = 18 relative to > or = 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.

Authors+Show Affiliations

Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9096391

Citation

Giovannucci, E, et al. "The CAG Repeat Within the Androgen Receptor Gene and Its Relationship to Prostate Cancer." Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 7, 1997, pp. 3320-3.
Giovannucci E, Stampfer MJ, Krithivas K, et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA. 1997;94(7):3320-3.
Giovannucci, E., Stampfer, M. J., Krithivas, K., Brown, M., Dahl, D., Brufsky, A., Talcott, J., Hennekens, C. H., & Kantoff, P. W. (1997). The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 94(7), 3320-3.
Giovannucci E, et al. The CAG Repeat Within the Androgen Receptor Gene and Its Relationship to Prostate Cancer. Proc Natl Acad Sci USA. 1997 Apr 1;94(7):3320-3. PubMed PMID: 9096391.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. AU - Giovannucci,E, AU - Stampfer,M J, AU - Krithivas,K, AU - Brown,M, AU - Dahl,D, AU - Brufsky,A, AU - Talcott,J, AU - Hennekens,C H, AU - Kantoff,P W, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 3320 EP - 3 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 94 IS - 7 N2 - 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 < or = 18 relative to > or = 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. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/9096391/The_CAG_repeat_within_the_androgen_receptor_gene_and_its_relationship_to_prostate_cancer_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&amp;pmid=9096391 DB - PRIME DP - Unbound Medicine ER -