Elsevier

Urology

Volume 53, Issue 1, January 1999, Pages 121-125
Urology

Adult Urology
The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia

https://doi.org/10.1016/S0090-4295(98)00468-3Get rights and content

Abstract

Objectives. Shorter CAG repeat lengths in exon 1 of the androgen receptor (AR) gene are associated with a stronger transcriptional activity of the AR and with a higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that men with shorter AR gene CAG repeat lengths have an increased risk of developing BPH.

Methods. Using data from the Health Professionals Follow-up Study (HPFS), we evaluated the relationship between AR gene CAG repeat length and prevalent BPH, as defined by BPH surgery, by enlarged prostate gland detected by digital rectal examination, and by urinary symptoms as determined by the American Urological Association Symptom Index.

Results. The odds ratio for BPH surgery or enlarged prostate gland was 1.92 (95% confidence interval [CI] 1.22 to 3.03; P [trend] = 0.0002), comparing AR gene CAG repeat length of 19 or less to 25 or more. Results were similar for the end points of BPH surgery (P [trend] = 0.002) and for enlarged prostate gland (P [trend] = 0.001). For a six-repeat decrease in CAG repeat length, the odds ratio for having moderate or severe urinary obstructive symptoms from an enlarged prostate gland was 3.62 (95% CI 1.51 to 8.67; P = 0.004).

Conclusions. Variability in the AR gene CAG repeat influences the development of symptomatic BPH, particularly in predicting obstructive urinary symptoms. Our findings support further study to establish the appropriate clinical relevance.

Section snippets

Material and methods

The Health Professionals Follow-up Study (HPFS) is an ongoing prospective cohort study among 51,529 male dentists, veterinarians, pharmacists, optometrists, osteopathic physicians, and podiatrists, aged 40 to 75 years old at enrollment in 1986. At baseline and every 2 years the men provided information on demographics, lifestyle factors, diet, and medical history. In 1993 we asked participants to provide a blood specimen. Approximately 18,000 men sent back blood specimens in vacutainer tubes

Results

The range of AR gene CAG repeats was 14 to 39 among 449 controls and 8 to 50 among 449 cases. There was a tendency for cases to have shorter AR gene CAG repeat lengths (P = 0.0006; Wilcoxon test, two-sided). The mean CAG repeat length was identical (21.6) for men with surgery for BPH or men without surgery but an enlarged prostate gland. The nine lowest values (less than 14) for AR gene CAG repeat lengths occurred among cases. For shorter repeat lengths, the OR was increased for men with

Comment

We found an inverse correlation between AR gene CAG repeat length and prevalence of surgery for BPH and enlarged prostate, determined either by DRE or a history of surgery for BPH. Men with AR gene CAG repeat lengths of 19 or less had an OR of BPH of 1.92 relative to men with repeat lengths of 25 or more. From a population perspective, the impact of AR gene CAG repeat length risk is substantial (see Fig. 1). These findings indicate that possessing an AR with greater transcriptional ability

Conclusions

AR gene CAG repeat length contributes to a man’s risk of developing BPH. The impact is substantial from a population perspective. The relation between CAG repeat lengths and BPH was particularly strong for obstructive symptoms, suggesting possible clinical utility.

References (20)

There are more references available in the full text version of this article.

Cited by (105)

  • Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men

    2014, European Urology
    Citation Excerpt :

    We included nine case-control studies, of which all but one contributed to meta-analysis. This meta-analysis demonstrates a marked Proteus effect [51], with the original papers based on US populations demonstrating a significant association between short CAG repeats and LUTS [52,53], which despite repeated studies was never replicated. In this instance the initial estimates of a significant association may have resulted from unaddressed population stratification.

  • CAG repeat testing of androgen receptor polymorphism: Is this necessary for the best clinical management of hypogonadism?

    2013, Journal of Sexual Medicine
    Citation Excerpt :

    The binding of these coactivators is modulated by the length of CAG repeats, which is the mechanism by which the repeat polymorphism is suspected to influence the transcriptional activity of target genes [29]. The influence of the CAG repeats on prostate size in eugonadal men has been investigated by several cross‐sectional studies [35]. Also, androgen substitution therapy in hypogonadal men demonstrates the impressive modulation by the CAG repeat polymorphism of prostate size and growth.

  • Endocrinology and Aging

    2011, Williams Textbook of Endocrinology, Twelfth Edition
  • Impact of androgen receptor cytosine-adenine-guanine polymorphisms on clinical outcome in BRCA mutation-associated epithelial ovarian cancers

    2010, Gynecologic Oncology
    Citation Excerpt :

    Patient data were abstracted from medical records and included surgical and pathologic findings and time to recurrence and death. For statistical considerations, a short AR allele length was defined as < 19 CAG repeats, consistent with published criteria implicating AR allelotype length in prostate and ovarian cancer prognosis [2,9]. We calculated a sample size analysis based upon the differences in survival observed in our previous unselected cohort [2].

View all citing articles on Scopus

Support for this project was from NIH Cancer Research grants CA55075, CA72036, and DK45779 and from the Dana Farber Cancer Institute Prostate Cancer Research Fund.

View full text