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Open Access Research article

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

Hui-Tzu Chen2, Yao-Chung Wu12, Shou-Tung Chen1, Hsien-Chang Tsai2 and Yi-Chih Chien2*

Author Affiliations

1 Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan

2 Department of Biology, National Changhua University of Education, No.1, Jin-De Road, 50058 Changhua City, Taiwan

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BMC Cancer 2014, 14:144  doi:10.1186/1471-2407-14-144

Published: 1 March 2014

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.

Keywords:
Breast cancer; Androgen receptor; Non-random X-chromosome inactivation; Loss of heterozygosity; Xq25