人乳腺癌易感基因突变和卵巢储备下降的探讨

Breast cancer susceptibility gene mutations and decreased ovarian reserve

人乳腺癌易感基因(BRCA)1和BRCA2的表达产物BRCA1和BRCA2蛋白是毛细血管扩张性共济失调突变基因(ATM)介导的DNA损伤修复信号通路成员,对DNA双链断裂同源重组修复至关重要。BRCA突变很大程度上增加了女性罹患乳腺癌、卵巢癌的风险。但对于BRCA突变产生的非癌症影响仍旧知之甚少。近年来有研究表明BRCA突变携带的女性可能出现卵巢储备下降。若BRCA突变与卵巢储备下降存在因果关系,则不仅有助于揭示遗传参与的卵巢衰老机制,甚至提示BRCA有望作为卵巢早衰的易感因素之一,有助于卵巢早衰的早期诊断。本文就近年来国内外的相关研究,对BRCA突变和卵巢储备功能下降作一探讨。

Breast cancer susceptibility gene（BRCA）1 and BRCA2 are menbers of the ATM-mediated DNA damage signalling pathway which are integral in the repair of DNA double strand breaks through homologous recombination. BRCA germline mutations substantially increase the risk of breast and ovarian cancer. But the non-cancer-related implications still remain less-known. A number of studies suggest that ovarian reserve may be reduced in BRCA mutation carriers. If the causal relationship between BRCA mutations and diminished ovarian reserve（DOR） is confirmed, it helps not only to recover the mechanism of ovarian aging but also the early diagnosis for premature ovarian failure（POF）. Here is to make a review of the reseach status of BRCA germline mutation and diminished ovarian reserve.