Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility
Androgen receptor gene CAG repeats, estrogen exposure status, and breast cancer susceptibility
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DOI：
10.1097/cej.0b013e3282f75e7f
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发表时间：
2008-08-01
影响因子：
2.4
通讯作者：
Sun, Chien-An
中科院分区：
文献类型：
--
作者：
Wu, Mei-Hsuan;Chou, Yu-Ching;Sun, Chien-An
雄激素受体（AR）外显子1中多态性CAG重复序列的长度与AR反式激活活性呈负相关。由于增强的雄激素刺激麦芽对抗由AR介导的乳腺细胞增殖，我们研究了AR-CAG重复序列长度是否与乳腺癌易感性相关。摘要本研究以台湾地区女性为研究对象，以1992年至2000年间88例新诊断乳癌病例为研究对象，并以334例配对对照为研究对象，进行巢式病例对照研究。通过标准化问卷调查获得危险因素，并收集血液样本，用于确定AR-CAG重复次数。携带一个或多个长AR（CAG）（n）重复等位基因（> 22个重复）的女性患乳腺癌的风险没有显著增加[比值比（OR），1.52; 95%可信区间（CI），0.80-2.90]。特别令人感兴趣的是，与长等位基因AR基因型相关的风险显著增加，该基因型主要存在于持续时间较短的女性中。（< 10年）早期雌激素暴露，如初潮年龄与首次足月妊娠年龄之间的间隔所示，与短AR等位基因基因型相比，（OR，2.70; 95%CI，1.00-731），尽管在长期早期雌激素暴露的女性中没有检测到这种显著相关性（OR，0.70; 95%CI，0.25-1.59）。这些数据表明，较长的AR（CAG）（n）重复等位基因可能会增加特定亚群个体患乳腺癌的风险，尽管这些发现需要在其他人群中复制。
The length of a polymorphic CAG repeat in exon 1 of the androgen receptor (AR) is inversely correlated with AR transactivation activity. As heightened androgenic stimulation malt oppose breast cell proliferation, which is mediated by AR, we examined whether AR-CAG repeat lengths are related to breast cancer susceptibility. A nested case-control study of 88 newly diagnosed cases of breast cancer between 1992 and 2000 and 334 matched controls was carried out in Taiwanese women. Risk factors were obtained through a standardized questionnaire interview and blood samples were collected and used to determine the number of AR-CAG repeats. Women with one or more long AR (CAG)(n) repeat alleles (> 22 repeats) were not at significantly increased risk of breast cancer [odds ratio (OR), 1.52; 95% confidence interval (Cl), 0.80-2.90]. Of particular interest was a significantly increased risk associated with the long-allele AR genotype that was present mostly among women with a short duration (< 10 years) of early estrogen exposure, as indicated by the interval between age at menarche and age at first full-term pregnancy, as compared with short AR allele genotypes (OR, 2.70; 95% Cl, 1.00-731), although no such significant association in women with a long duration of early estrogen exposure (OR, 0.70; 95% Cl, 0.25-1.59) was detected. These data suggest that longer AR (CAG)(n) repeat alleles may confer an increased risk of breast cancer among particular subsets of individuals, although these findings need replication in other populations.