The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer

Given, H. F.; Radbourne, R.; Oag, H.; Merritt, Samantha; Barclay, Ella; Hanby, Andrew M.; Lamlum, Hanan; McGrath, J.P.; Curran, Catherine; Tomlinson, I.

doi:10.1016/s0959-8049(99)00310-x

Cited by 20 publications

(10 citation statements)

References 6 publications

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“…Several studies investigated these polymorphic repeats separately in diVerent pathologies including breast cancer, but to our knowledge, no one investigated them together till date. Association studies between AR CAG repeat length and breast cancer displayed inconsistent results, some reporting a strong association between long CAG repeats and breast cancer (Rebbeck et al 1999;Haiman et al 2002;Elhaji et al 2001;Giguere et al 2001;Yu et al 2000) while other studies showing no association (Spurdle et al 1999;Kadouri et al 2001;Menin et al 2001;Given et al 2000;Dagan et al 2002), although in vitro studies demonstrated that long fragments of CAG repeats are associated with a low function of the AR (Chamberlain et al 1994;Irvine et al 2000). Investigating the potential role of CAG repeats in female breast cancer is diYcult because of the presence of two alleles and the random chromosome X inactivation.…”

Section: Discussionmentioning

confidence: 99%

Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

Anghel

Raica

Marian

et al. 2006

J Cancer Res Clin Oncol

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Section: Discussionmentioning

confidence: 99%

Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

Anghel

Raica

Marian

et al. 2006

J Cancer Res Clin Oncol

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“…Longer (X28) CAG repeats have also been associated with a lower age at diagnosis of breast cancer in women with germline BRCA1 mutations, 54 although this was not substantiated in a study of early-onset breast cancer. 55 Alternatively, the finding that shorter CAG repeats is associated with a reduced risk might be related to an as yet unknown negative feedback mechanism, whereby reduced growth stimuli caused by longer AR CAG repeats disrupt this loop causing cells to overcompensate, thus leading to earlier onset CaP.…”

Section: Discussionmentioning

confidence: 99%

Association between hormonal genetic polymorphisms and early-onset prostate cancer

Forrest

Edwards

Houlston

et al. 2005

Prostate Cancer Prostatic Dis

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We investigated the association between seven polymorphisms in four candidate genes involved in vitamin D and androgen metabolism with early-onset prostate cancer (CaP) risk. The polymorphisms were genotyped in 288 UK males who were diagnosed with CaP at the age of 55 y or younger and up to 700 population-based controls. An additional 50 cases (not selected for age) and 76 controls were also genotyped. Short (p22 repeats) AR (CAG) n repeats were associated with a significantly reduced risk of early onset CaP (OR 0.68, 95% CI 0.50-0.91) compared with men with long (422) repeats. Men homozygous for the leucine variant of SRD5A2 p.89V4L were also found to be at a significantly increased risk of CaP compared with men who were homozygous for the valine allele (OR 1.84, 95% CI 1.15-2.98). No associations were found with the AR (GGC) n , CYP17 Msp A1 I, VDR Taq I, SRD5A2 (TA) n and p.49A4T polymorphisms and CaP risk. These findings suggest that common polymorphisms in the AR and SRD5A2 genes may be associated with early-onset CaP in British men.

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“…In prostate, a number of studies have identified an association between short CAG repeat length and the risk or severity of prostate cancer [15]. More recently, studies on AR CAG repeat length and breast cancer in women have reported conflicting results, with some reports showing an association between long CAG repeats and breast cancer [16][17][18][19][20], but other studies showing no association [21][22][23][24][25]. The AR gene is on the X chromosome, therefore the identification of the potential role of CAG repeat length in female breast cancer is complicated by the presence of two alleles, and random X-inactivation.…”

Section: Introductionmentioning

confidence: 99%

Increased frequency of long androgen receptor CAG repeats in male breast cancers

MacLean

Brown²,

Beilin

et al. 2004

Breast Cancer Res Treat

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We have investigated the possible link between androgen hyposensitivity caused by long androgen receptor (AR) CAG repeats, and breast carcinogenesis, in men. AR gene mutations have been described in men with androgen insensitivity syndrome and breast carcinoma, and some studies have shown long CAG repeats are associated with increased risk of breast cancer in women. DNA was isolated from male breast cancer biopsies, and the AR CAG repeat sized. Forty one male breast cancer samples were studied, including one sample from a man with spinal and bulbar muscular atrophy (SBMA), which is caused by an AR CAG repeat expansion. The man with breast cancer and SBMA had 49 CAG repeats (normal range 6-35), but all other breast cancer samples had repeats within the normal range. The frequency of CAG repeats > or =24 was significantly higher in the breast cancer group (excluding the SBMA subject) than in the normal population (p<0.05), and was more marked in grade I and II tumors (p=0.001). There was no correlation between AR CAG repeat length and age at diagnosis. In conclusion, longer AR CAG repeats are more common in men with breast cancer than in the control male population. Androgen hyposensitivity, caused by long AR CAG repeats, may increase the risk of breast cancer in men.

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The androgen receptor exon 1 trinucleotide repeat does not act as a modifier of the age of presentation in breast cancer

Cited by 20 publications

References 6 publications

Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

Association between hormonal genetic polymorphisms and early-onset prostate cancer

Increased frequency of long androgen receptor CAG repeats in male breast cancers

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