Sasaki Masahiro, Kaneuchi Masanori, Sakuragi Noriaki, Fujimoto Seiichiro, Carroll Peter R, Dahiya Rajvir
Department of Urology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA.
Biochem Biophys Res Commun. 2003 Dec 26;312(4):1244-7. doi: 10.1016/j.bbrc.2003.11.075.
Human androgen receptor (AR) gene contains two polymorphic trinucleotide repeats of CAG and GGC, which code for polyglutamine and polyglycine tracts in the N-terminal domain in which the receptor activity resides. Longer repeats induce decrease of transactivation function in the AR receptor, weaken an anti-proliferative effect on various steroid-related tissues, and may promote the carcinogenesis of these cancers, such as breast, endometrial, and ovarian cancers. However, the incidences of these steroid-related cancers are remarkably lower in Japanese than in Caucasians. We hypothesize that the GGC and CAG repeats in AR gene correspond to lower incidence of steroid-related cancers in the Japanese population. To test this hypothesis, these two polymorphic trinucleotide repeats in AR gene were genotyped in 221 Japanese and 177 Caucasians. The results of genotyping in these loci clearly show that the distribution of GGC repeat is significantly different between these populations (P<0.001). Japanese (73.7%) had 16 GGC repeats compared to 53.3% for Caucasians. Japanese (3.8%) also had 17 GGC repeats compared to 36.2% for Caucasians. No Japanese had more than 18 GGC repeats compared to 3.4% for Caucasians. The length of CAG repeats in the Japanese population was not significantly different than that of the Caucasian population, although the CAG repeats varied from 14 to 31 and 15 to 29 repeats in Japanese and German populations, respectively. This study demonstrates that the Japanese population has shorter GGC compared to the Caucasian population, which may explain the incidences of estrogen-related cancers in these populations.
人类雄激素受体（AR）基因包含两个多态性三核苷酸重复序列，即CAG和GGC，它们编码位于N端结构域的多聚谷氨酰胺和多聚甘氨酸序列，而受体活性就存在于该结构域。较长的重复序列会导致AR受体的反式激活功能降低，削弱对各种类固醇相关组织的抗增殖作用，并可能促进这些癌症的发生，如乳腺癌、子宫内膜癌和卵巢癌。然而，这些类固醇相关癌症的发病率在日本人中明显低于白种人。我们推测，AR基因中的GGC和CAG重复序列与日本人群中类固醇相关癌症的低发病率相对应。为了验证这一推测，我们对221名日本人及177名白种人的AR基因中的这两个多态性三核苷酸重复序列进行了基因分型。这些位点的基因分型结果清楚地表明，GGC重复序列在这两个人群中的分布存在显著差异（P<0.001）。日本人中73.7%有16个GGC重复序列，而白种人中这一比例为53.3%。日本人中3.8%有17个GGC重复序列，而白种人中这一比例为36.2%。没有日本人的GGC重复序列超过18个，而白种人中这一比例为3.4%。日本人群中CAG重复序列的长度与白种人群没有显著差异，尽管日本人群中CAG重复序列的范围为14至31个，而德国人群中为15至29个。这项研究表明，与白种人群相比，日本人群的GGC重复序列较短，这可能解释了这两个人群中雌激素相关癌症的发病率差异。
