Association between estrogen and androgen receptor genes and prostate cancer risk

ObjectiveProstate cancer (PC) is one of the principal causes of death among men. Steroid hormones are involved in normal prostate growth and carcinogenesis. The purpose of our study was to investigate the effects on PC risk of polymorphisms from three steroid hormone receptor genes: the androgen (AR), and the α (ESR1) and β (ESR2) estrogen receptors.Design and methodsThe study was performed on a Caucasian population of 1045 PC patients and 814 controls. Using a logistic regression model, the different alleles and genotypes from those polymorphisms were analyzed according to case/control status, the tumor aggressiveness, and the age at onset.ResultsA significant association between PC risk and the pooled 4/5, 5/6, and 6/6 genotypes of the GGGA repeat located in the first intron of ESR1 (odds ratio (OR)=3.00, 95% CI=1.32–6.82, P=0.008) was observed. When we stratified the cases, this association was confined to patients with a Gleason score of 2–4 (OR=8.34, 95% CI=2.91–23.91, P<0.0001) or late onset PC (OR=2.91, 95% CI=1.22–6.93, P=0.016). An association between a short AR CAG repeat (less than 17 repeats) was also observed among patients with late onset PC (OR=2.34, 95% CI=1.15–4.76, P=0.019).ConclusionsThese findings suggest that the GGGA repeat from ESR1 and the CAG repeat from AR may be associated with risk of late onset PC.

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Faculty Opinions recommendation of Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725966457.793519610 ◽

2016 ◽

Author(s):

Charlotte Bevan ◽

Greg Brooke

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Candidate Genes ◽

Prostate Cancer Risk ◽

Prostate Tissue ◽

Data Set ◽

Normal Prostate ◽

Risk Snps ◽

Normal Prostate Tissue ◽

Eqtl Data

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An expanded variant list and assembly annotation identifies multiple novel coding and noncoding genes for prostate cancer risk using a normal prostate tissue eQTL data set

PLoS ONE ◽

10.1371/journal.pone.0214588 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0214588

Author(s):

Melissa S. DeRycke ◽

Melissa C. Larson ◽

Asha A. Nair ◽

Shannon K. McDonnell ◽

Amy J. French ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Prostate Cancer Risk ◽

Prostate Tissue ◽

Data Set ◽

Normal Prostate ◽

Normal Prostate Tissue ◽

Eqtl Data

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Abstract B49: Androgen receptor CAG repeat length association with prostate cancer risk in obese and non-obese African American men

10.1158/1538-7755.disp13-b49 ◽

2014 ◽

Author(s):

Ganna Chornokur ◽

Ernest K. Amankwah ◽

Jong Y. Park ◽

Catherine M. Phelan ◽

Julio Powsang ◽

...

Keyword(s):

Prostate Cancer ◽

African American ◽

Androgen Receptor ◽

Cancer Risk ◽

African American Men ◽

Prostate Cancer Risk ◽

Repeat Length ◽

Cag Repeat

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Cag Repeat Number in the Androgen Receptor Gene and Prostate Cancer

Balkan Journal of Medical Genetics ◽

10.2478/v10034-012-0005-z ◽

2012 ◽

Vol 15 (1) ◽

pp. 31-36 ◽

Cited By ~ 6

Author(s):

S Madjunkova ◽

A Eftimov ◽

V Georgiev ◽

D Petrovski ◽

A Dimovski ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Risk ◽

Receptor Gene ◽

Prostate Cancer Risk ◽

Androgen Receptor Gene ◽

Repeat Length ◽

Cag Repeat ◽

Cag Repeats ◽

Repeat Number

Cag Repeat Number in the Androgen Receptor Gene and Prostate CancerProstate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5' end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ±2.65, in controls 22.28 ±2.86 (p = 0.009) and in BPH patients 22.1 ±2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men.

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Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer

Endocrine Related Cancer ◽

10.1677/erc-07-0078 ◽

2007 ◽

Vol 14 (3) ◽

pp. 645-654 ◽

Cited By ~ 21

Author(s):

S Leskelä ◽

E Honrado ◽

C Montero-Conde ◽

I Landa ◽

A Cascón ◽

...

Keyword(s):

Prostate Cancer ◽

Cytochrome P450 ◽

Prostate Cancer Risk ◽

Cytochrome P450 3A ◽

Active Metabolites ◽

Normal Prostate ◽

Prostate Cells ◽

Mrna Content ◽

Luminal Cells ◽

And Function

Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.

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