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绝经后结肠癌中雌激素受体-β 基因胞嘧啶-腺嘌呤(-CA)重复多态性。

Estrogen Receptor-β Gene Cytosine-Adenine (-CA) Repeat Polymorphism in Postmenopausal Colon Cancer.

机构信息

Department of Pathology, Faculty of Medicine, Toho University, Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan.

Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo 135-8550, Japan.

出版信息

Int J Mol Sci. 2023 Feb 24;24(5):4502. doi: 10.3390/ijms24054502.

Abstract

The pathobiological role of estrogen is controversial in colorectal cancer. Cytosine-adenine (CA) repeat in the estrogen receptor (ER)-β gene (-CA) is a microsatellite, as well as representative of polymorphism. Though its function is unknown, we previously showed that a shorter allele (germline) increased the risk of colon cancer in older women, whereas it decreased it in younger postmenopausal women. -CA and ER-β expressions were examined in cancerous (Ca) and non-cancerous (NonCa) tissue pairs from 114 postmenopausal women, and comparisons were made considering tissue types, age/locus, and the mismatch repair protein (MMR) status. -CA repeats <22/≥22 were designated as 'S'/'L', respectively, resulting in genotypes SS/nSS (=SL&LL). In NonCa, the rate of the SS genotype and ER-β expression level were significantly higher in right-sided cases of women ≥70 (≥70Rt) than in those in the others. A decreased ER-β expression in Ca compared with NonCa was observed in proficient-MMR, but not in deficient-MMR. In NonCa, but not in Ca, ER-β expression was significantly higher in SS than in nSS. ≥70Rt cases were characterized by NonCa with a high rate of SS genotype or high ER-β expression. The germline -CA genotype and resulting ER-β expression were considered to affect the clinical characteristics (age/locus/MMR status) of colon cancer, supporting our previous findings.

摘要

雌激素在结直肠癌中的病理生物学作用存在争议。雌激素受体(ER)-β 基因中的胞嘧啶-腺嘌呤(CA)重复序列(-CA)是一种微卫星,也是多态性的代表。尽管其功能尚不清楚,但我们之前的研究表明,较短的等位基因(胚系)增加了老年女性患结肠癌的风险,而在年轻绝经后女性中则降低了这种风险。我们检测了 114 例绝经后女性的癌组织(Ca)和非癌组织(NonCa)配对中的 -CA 和 ER-β 表达,并考虑了组织类型、年龄/部位和错配修复蛋白(MMR)状态进行了比较。-CA 重复次数<22/≥22 分别指定为'S'/'L',从而产生 SS/nSS(=SL&LL)基因型。在 NonCa 中,≥70 岁(≥70Rt)的女性右侧病例中 SS 基因型和 ER-β 表达水平的发生率明显高于其他女性。在功能正常的 MMR 中,Ca 中 ER-β 表达水平明显低于 NonCa,但在功能缺陷的 MMR 中则没有。在 NonCa 中,SS 基因型的 ER-β 表达明显高于 nSS。≥70Rt 病例的特点是非癌组织中 SS 基因型或 ER-β 表达水平较高。胚系 -CA 基因型和由此产生的 ER-β 表达被认为会影响结肠癌的临床特征(年龄/部位/MMR 状态),这支持了我们之前的研究结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c69/10003297/51c457d2e836/ijms-24-04502-g001.jpg

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