Adult UrologyThe CAG repeat within the androgen receptor gene and benign prostatic hyperplasia☆
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)
- et al.
Evolving patterns of tissue composition in benign prostatic hyperplasia as a function of specimen size
Hum Pathol
(1990) - et al.
The American Urological Association symptom index for benign prostatic hyperplasia
J Urol
(1992) - et al.
Distinction between symptoms of voiding and filling in benign prostatic hyperplasiafindings from the Health Professionals Follow-up Study
Urology
(1998) - et al.
Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck
Br J Urol
(1975) Importance of the natural history of benign prostatic hyperplasia in the evaluation of pharmacologic intervention
Prostate
(1990)- et al.
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy
Nature
(1991) - et al.
Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy
Neurology
(1992) - et al.
Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility
J Clin Endocrinol Metab
(1997) - et al.
The length and location of CAG trinucleotide repeats in the androgen N-terminal domain affect transactivation function
Nucleic Acids Res
(1994) - et al.
Evidence for a repressive function of the long polyglutamine tract in the human androgen receptorpossible pathogenetic relevance for the (CAG)n-expanded neuronopathies
Hum Mol Genet
(1995)
Cited by (105)
Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men
2014, European UrologyCitation 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 MedicineCitation 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.
Androgens and estrogens in benign prostatic hyperplasia: Past, present and future
2011, DifferentiationEndocrinology and Aging
2011, Williams Textbook of Endocrinology, Twelfth EditionImpact of androgen receptor cytosine-adenine-guanine polymorphisms on clinical outcome in BRCA mutation-associated epithelial ovarian cancers
2010, Gynecologic OncologyCitation 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].
- ☆
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.