子宫内膜癌患者雄激素受体基因上的GGC和StuI多态性

GGC and StuI polymorphism on the androgen receptor gene in endometrial cancer patients.

作者信息

Sasaki Masahiro, Karube Akihiro, Karube Yuko, Watari Michiko, Sakuragi Noriaki, Fujimoto Seiichiro, Dahiya Rajvir

机构信息

Department of Urology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA.

出版信息

Biochem Biophys Res Commun. 2005 Apr 1;329(1):100-4. doi: 10.1016/j.bbrc.2005.01.104.

DOI:10.1016/j.bbrc.2005.01.104

PMID:15721279

Abstract

Androgens have an anti-proliferative effect on endometrial cells. Human androgen receptor (AR) gene contains two polymorphic short tandem repeats of GGC and CAG, and a single-nucleotide polymorphism on exon 1 that is recognized by the restriction enzyme, StuI. Prior studies have shown that the lengths of the CAG repeat are inversely and linearly related to AR activity and associated with endometrial cancer. However, little is known about the GGC repeat and the StuI polymorphism of the AR gene. Thus, we investigated whether these AR polymorphisms are risk factors for endometrial cancer. To test this hypothesis, the genetic distributions of these polymorphisms were investigated in blood samples from endometrial cancer patients and healthy controls. The allelic and genotyping profiles were analyzed by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and direct DNA sequencing, and analyzed statistically. The GGC repeat was significantly longer in endometrial cancer patients as compared to normal healthy controls. In general, an increased risk of endometrial cancer was found with increasing GGC repeat. The relative risk for the 17 GGC repeat was greater than 4, as compared to controls. However, the StuI polymorphism was not significantly different between patients and controls. The findings suggest that increased numbers of GGC repeat on the AR gene may be a risk factor for endometrial cancer.

摘要

雄激素对子宫内膜细胞具有抗增殖作用。人类雄激素受体（AR）基因包含两个GGC和CAG的多态性短串联重复序列，以及外显子1上的一个单核苷酸多态性，该多态性可被限制性内切酶StuI识别。先前的研究表明，CAG重复序列的长度与AR活性呈反比且呈线性关系，并与子宫内膜癌相关。然而，关于AR基因的GGC重复序列和StuI多态性知之甚少。因此，我们研究了这些AR多态性是否为子宫内膜癌的危险因素。为了验证这一假设，我们在子宫内膜癌患者和健康对照者的血液样本中研究了这些多态性的基因分布。通过聚合酶链反应（PCR）、PCR-限制性片段长度多态性（PCR-RFLP）和直接DNA测序分析等位基因和基因分型谱，并进行统计学分析。与正常健康对照相比，子宫内膜癌患者的GGC重复序列明显更长。一般来说，随着GGC重复序列的增加，子宫内膜癌的风险增加。与对照组相比，17个GGC重复序列的相对风险大于4。然而，患者和对照组之间的StuI多态性没有显著差异。研究结果表明，AR基因上GGC重复序列数量的增加可能是子宫内膜癌的一个危险因素。