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Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression.
J Urol. 2000 Aug; 164(2):567-72.JU

Abstract

PURPOSE

The CAG repeat polymorphism of the androgen receptor gene has been associated with an increased prostate cancer risk, and the repeat length correlated with cancer stage and grade at presentation. Men with an allele length of </= 18 CAG repeats have a 2-fold increase in risk for high-stage or high-grade prostate cancer, compared with patients with a longer CAG repeat. We examined the significance of the CAG repeat polymorphism of the androgen receptor gene for predicting prostate cancer progression among 318 patients treated by radical prostatectomy for clinically localized prostate cancer between 1987 and 1994.

MATERIALS AND METHODS

Leukocyte DNA was collected and genotyping of the CAG repeat polymorphism was performed using a PCR-based direct sequencing method. Risk ratios were calculated for developing biochemical recurrence for patients associated with an allele length of </= 18 CAG repeats, compared with patients with an allele length of >18 CAG repeats, controlling for grade, stage and serum PSA level at diagnosis using Cox proportional hazard modeling.

RESULTS

Overall, the CAG repeat allele was not predictive of recurrence; tumor grade, stage and PSA level at diagnosis were the only predictors of recurrence in a multivariate analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6, stage pT2, and PSA </= 10 ng./ml.), the relative risk of recurrence associated with an allele of </= 18 CAG repeats was 8.07 (95% C.I., 2.02 to 32.2, p = 0.004), compared with patients with an allele length of >18 CAG repeats. In contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage pT3/4, or PSA >10 ng./ml.), the relative risk associated with the </= 18 CAG repeat allele was 0.72 (95% C.I., 0.33 to 1.57, p = 0.41), compared with patients with the >18 CAG repeat allele.

CONCLUSIONS

The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments.

Authors+Show Affiliations

Divisions of Urology, Pathology, and Medicine and the Clinical Epidemiology Health Services Research Unit, Toronto General Hospital/Princess Margaret Hospital, Ontario, Canada.No affiliation info availableNo 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

Language

eng

PubMed ID

10893645

Citation

Nam, R K., et al. "Significance of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Prostate Cancer Progression." The Journal of Urology, vol. 164, no. 2, 2000, pp. 567-72.
Nam RK, Elhaji Y, Krahn MD, et al. Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression. J Urol. 2000;164(2):567-72.
Nam, R. K., Elhaji, Y., Krahn, M. D., Hakimi, J., Ho, M., Chu, W., Sweet, J., Trachtenberg, J., Jewett, M. A., & Narod, S. A. (2000). Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression. The Journal of Urology, 164(2), 567-72.
Nam RK, et al. Significance of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Prostate Cancer Progression. J Urol. 2000;164(2):567-72. PubMed PMID: 10893645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression. AU - Nam,R K, AU - Elhaji,Y, AU - Krahn,M D, AU - Hakimi,J, AU - Ho,M, AU - Chu,W, AU - Sweet,J, AU - Trachtenberg,J, AU - Jewett,M A, AU - Narod,S A, PY - 2000/7/14/pubmed PY - 2000/9/19/medline PY - 2000/7/14/entrez SP - 567 EP - 72 JF - The Journal of urology JO - J. Urol. VL - 164 IS - 2 N2 - PURPOSE: The CAG repeat polymorphism of the androgen receptor gene has been associated with an increased prostate cancer risk, and the repeat length correlated with cancer stage and grade at presentation. Men with an allele length of </= 18 CAG repeats have a 2-fold increase in risk for high-stage or high-grade prostate cancer, compared with patients with a longer CAG repeat. We examined the significance of the CAG repeat polymorphism of the androgen receptor gene for predicting prostate cancer progression among 318 patients treated by radical prostatectomy for clinically localized prostate cancer between 1987 and 1994. MATERIALS AND METHODS: Leukocyte DNA was collected and genotyping of the CAG repeat polymorphism was performed using a PCR-based direct sequencing method. Risk ratios were calculated for developing biochemical recurrence for patients associated with an allele length of </= 18 CAG repeats, compared with patients with an allele length of >18 CAG repeats, controlling for grade, stage and serum PSA level at diagnosis using Cox proportional hazard modeling. RESULTS: Overall, the CAG repeat allele was not predictive of recurrence; tumor grade, stage and PSA level at diagnosis were the only predictors of recurrence in a multivariate analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6, stage pT2, and PSA </= 10 ng./ml.), the relative risk of recurrence associated with an allele of </= 18 CAG repeats was 8.07 (95% C.I., 2.02 to 32.2, p = 0.004), compared with patients with an allele length of >18 CAG repeats. In contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage pT3/4, or PSA >10 ng./ml.), the relative risk associated with the </= 18 CAG repeat allele was 0.72 (95% C.I., 0.33 to 1.57, p = 0.41), compared with patients with the >18 CAG repeat allele. CONCLUSIONS: The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments. SN - 0022-5347 UR - https://www.unboundmedicine.com/medline/citation/10893645/Significance_of_the_CAG_repeat_polymorphism_of_the_androgen_receptor_gene_in_prostate_cancer_progression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-5347(05)67424-1 DB - PRIME DP - Unbound Medicine ER -