Racial Differences in Androgen Receptor Protein Expression in Men With Clinically Localized Prostate Cancer

Gaston, Kris E.; Kim, Desok; Singh, Shweta; Ford, O. Harris; Mohler, James L.

doi:10.1097/01.ju.0000079761.56154.e5

Cited by 118 publications

(104 citation statements)

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“…Consistent with the in vitro studies showing increased activity of the AR product with shorter AR CAG and GGN repeat alleles, studies have also found increased AR protein expression levels in prostatic tissues from men of African descent (Gaston et al 2003;Olapade-Olaopa et al 2004). Specifically, AR protein expression levels were estimated to be 22% higher in benign prostate cancer tissues and 81% higher in malignant prostate cancer tissues in African Americans versus Caucasian Americans (Gaston et al 2003).…”

Section: Introductionsupporting

confidence: 73%

“…Studies comparing the distribution of allele sizes for the CAG and GGN microsatellite repeat polymorphisms between different populations have noted shorter repeat lengths, on average, in men of African versus Caucasian descent (Kittles et al 2001;Esteban et al 2006). Consistent with the in vitro studies showing increased activity of the AR product with shorter AR CAG and GGN repeat alleles, studies have also found increased AR protein expression levels in prostatic tissues from men of African descent (Gaston et al 2003;Olapade-Olaopa et al 2004). Specifically, AR protein expression levels were estimated to be 22% higher in benign prostate cancer tissues and 81% higher in malignant prostate cancer tissues in African Americans versus Caucasian Americans (Gaston et al 2003).…”

Section: Introductionmentioning

confidence: 59%

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The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

et al. 2008

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Repeat lengths of the CAG and GGN microsatellites in exon 1 of the androgen receptor (AR) gene have been hypothesized to be associated with prostate cancer risk. In vitro studies have showed an inverse association between AR CAG and GGN repeat length and activity levels of the AR product. It is known that men of African descent have a higher incidence of and greater mortality from prostate cancer than men of Caucasian or Asian descent and, on average, a smaller number of repeats at AR CAG and GGN. Consistent with these findings, studies have also found increased AR protein expression levels in benign prostatic hyperplasia and prostatic diseased tissues from men of African descent. Despite these findings, limited studies have been conducted to evaluate the association between repeat lengths at AR CAG and prostate cancer risk in African Americans. Our study is the first such study to examine whether repeat length of the AR GGN repeat is associated with prostate cancer risk in African Americans. We found no evidence for an association between AR CAG or GGN repeat lengths and prostate cancer risk in a population-based sample of African Americans.

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Section: Introductionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 59%

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

et al. 2008

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“…14 Finally, increased androgen activity among black men was suggested by a study which found that benign and malignant prostate tissue from black men had both a greater number of cells staining positive for the androgen receptor as well as more intense staining within positive cells. 15 Although androgens regulate cellular PSA production they also affect prostate size. 16 Therefore, higher androgenicity among black men would be expected to result in larger sized prostates.…”

Section: Discussionmentioning

confidence: 99%

Do Racial Differences in Prostate Size Explain Higher Serum Prostate-Specific Antigen Concentrations Among Black Men?

Mavropoulos

Partin

Amling

et al. 2007

Urology

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Objectives-Black men have higher serum PSA values than white men. As levels of serum PSA directly correlate with prostate size, we hypothesized that elevated serum PSA values in black men may be due, at least partially, to larger prostate size among black men. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Methods-The NIH Public Access Author ManuscriptUrology. Author manuscript; available in PMC 2012 February 9. at the Johns Hopkins Hospital. We evaluated the association between race and serum PSA and prostate weight using multivariable linear regression while adjusting for demographic and clinicopathological cancer characteristics.Results-In both cohorts, black men had higher serum PSA values (p≤0.001). After adjusting for either demographic characteristics or demographic and cancer-specific characteristics, there were no significant associations between race and prostate size in either cohort. After adjusting for multiple demographic, clinical, and pathological cancer-specific characteristics, black men had 15% higher serum PSA values relative to white men in both the SEARCH (p=0.001) and Hopkins cohorts (p<0.001).Conclusions-In this study of patients undergoing radical prostatectomy in two very different practice settings, black men in both cohorts had higher serum PSA values relative to white men despite adjustment for demographic and cancer-specific characteristics, including prostate weight. The lack of significant association between race and prostate size suggests alternative reasons are needed to explain higher serum PSA levels in black men.

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“…[34] AR protein expression was evaluated in malignant and benign prostate tissue from African Americans and Caucasian Americans who underwent radical prostatectomy for clinically localized CaP. [35] Archived radical prostatectomy specimens obtained from 25 Caucasian Americans and 25 African Americans had AR protein antigen retrieved and immunostained. AR protein expression from CaP and benign tissue was assessed using two methods.…”

Section: Androgen Receptor and Racial Differences In Prostate Cancermentioning

confidence: 99%

A role for the androgen-receptor in clinically localized and advanced prostate cancer

Mohler

2008

Best Practice & Research Clinical Endocrinology & Metab

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Earlier studies of androgen-receptor (AR) expression using frozen prostate tissue, and later studies using archived specimens, produced the consensus that ligand-stabilized AR is nuclear, AR expression is similar in benign epithelia and stroma, AR expression is greater in secretory epithelia than basal cells, and AR expression is more variable in prostate cancer (CaP) than in benign prostatic hyperplasia (BPH). Accurate measurement of AR expression remains technically challenging but necessary to evaluate the relevance of ARs to clinical CaP. Recent studies demonstrated that AR expression in epithelia and stroma may be prognostic in clinically localized CaP, and AR expression may play a role in racial differences in CaP mortality and predict response to androgen deprivation therapy. High levels of AR and AR-regulated gene expression indicate a central role for AR in growth regulation of castration-recurrent CaP. New treatments for the lethal phenotype of CaP require better understanding of AR transactivation during androgen deprivation therapy. Keywordsandrogen receptor; prostate cancer; quantitative video image analysis; immunohistochemistry Androgens are necessary for the development and growth of the prostate and for the development, growth and progression of prostate cancer (CaP). An American man is diagnosed with CaP every 3 minutes,[1] and the worldwide incidence of CaP is increasing an estimated 1.1% annually.[2] Despite increased use of digital rectal examination and serum prostatespecific antigen (PSA) measurement for early detection, approximately 30% of men treated with curative intent suffer CaP recurrence. These men, and those who present with locally advanced or metastatic CaP, can be palliated by androgen deprivation therapy (ADT), which causes regression of androgen-dependent CaP through programmed cell death.[3] Although there are many methods for medical and surgical ADT, the results of ADT remain unimproved since its discovery more than 60 years ago.[4] More than 80% of men with disseminated CaP demonstrate clinical or biochemical response that is associated with a mean life expectancy of approximately 3.5 years, in contrast to non-responders or untreated patients who live an average of 9 months. Regardless of the androgen responsiveness of incurable CaP, almost all patients succumb to castration-recurrent CaP because it responds poorly to all known therapies, and

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Racial Differences in Androgen Receptor Protein Expression in Men With Clinically Localized Prostate Cancer

Abstract: AR protein expression was 22% higher in the benign prostate and 81% higher in the CaP of black African compared with white men. CaP may occur at a younger age and progress more rapidly in black than in white men due to racial differences in androgenic stimulation of the prostate.

Cited by 118 publications

References 15 publications

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

Do Racial Differences in Prostate Size Explain Higher Serum Prostate-Specific Antigen Concentrations Among Black Men?

A role for the androgen-receptor in clinically localized and advanced prostate cancer

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