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

BMC Cancer

Yi-Chih Chien¹  Hsien-Chang Tsai¹  Shou-Tung Chen²  Yao-Chung Wu¹  Hui-Tzu Chen¹ 

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

[2]Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan

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

Others  :  859012
DOI  :  10.1186/1471-2407-14-144

 received in 2013-08-22, accepted in 2014-02-26,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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