Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk

Hui Tzu Chen, Yao Chung Wu, Shou Tung Chen, Hsien Chang Tsai, Yi Chih Chien

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Abstract

Background: The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development.Methods: Seventy-nine breast cancer patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker.Results: LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).Conclusions: The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.

Original languageEnglish
Article number144
JournalBMC Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - 2014 Feb 1

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X Chromosome Inactivation
Loss of Heterozygosity
Androgen Receptors
Breast Neoplasms
Alleles
Microsatellite Repeats
Tumor Suppressor Genes
Genetic Markers
Lung Neoplasms
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Cite this

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title = "Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk",
abstract = "Background: The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development.Methods: Seventy-nine breast cancer patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker.Results: LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23{\%}). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).Conclusions: The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.",
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Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk. / Chen, Hui Tzu; Wu, Yao Chung; Chen, Shou Tung; Tsai, Hsien Chang; Chien, Yi Chih.

In: BMC Cancer, Vol. 14, No. 1, 144, 01.02.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Androgen receptor CAG repeats, non-random X chromosome inactivation, and loss of heterozygosity at Xq25 in relation to breast cancer risk

AU - Chen, Hui Tzu

AU - Wu, Yao Chung

AU - Chen, Shou Tung

AU - Tsai, Hsien Chang

AU - Chien, Yi Chih

PY - 2014/2/1

Y1 - 2014/2/1

N2 - Background: The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development.Methods: Seventy-nine breast cancer patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker.Results: LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).Conclusions: The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.

AB - Background: The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development.Methods: Seventy-nine breast cancer patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker.Results: LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).Conclusions: The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.

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