Research Laboratory on Human Reproduction, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Fertility Clinic, HUB-Erasme Hospital, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Int J Mol Sci. 2023 Dec 22;25(1):204. doi: 10.3390/ijms25010204.
Hereditary cancers mostly affect the adolescent and young adult population (AYA) at reproductive age. Mutations in () genes are responsible for the majority of cases of hereditary breast and ovarian cancer. and act as tumor suppressor genes as they are key regulators of DNA repair through homologous recombination. Evidence of the accumulation of DNA double-strand break has been reported in aging oocytes, while expression decreases, leading to the hypothesis that mutation may impact fertility. Moreover, patients exposed to anticancer treatments are at higher risk of fertility-related issues, and mutations could exacerbate the treatment-induced depletion of the ovarian reserve. In this review, we summarized the functions of both genes and reported the current knowledge on the impact of mutations on ovarian ageing, premature ovarian insufficiency, female fertility preservation strategies and insights about male infertility. Altogether, this review provides relevant up-to-date information on the impact of mutations on fertility. Notably, -mutated patients should be adequately counselled for fertility preservation strategies, considering their higher sensitivity to chemotherapy gonadotoxic effects.
遗传性癌症主要影响生殖年龄的青少年和年轻成年人群（AYA）。（）基因突变是遗传性乳腺癌和卵巢癌的大多数病例的原因。和作为肿瘤抑制基因发挥作用，因为它们是通过同源重组进行 DNA 修复的关键调节剂。已经有报道称，衰老的卵母细胞中积累了 DNA 双链断裂，而表达下降，导致假设突变可能会影响生育能力。此外，接受抗癌治疗的患者患与生育相关问题的风险更高，并且突变可能会加剧治疗引起的卵巢储备耗竭。在这篇综述中，我们总结了这两个基因的功能，并报告了目前关于突变对卵巢衰老、卵巢早衰、女性生育力保存策略的影响的知识，以及对男性不育的见解。总的来说，这篇综述提供了关于突变对生育能力影响的相关最新信息。值得注意的是，-突变患者应充分考虑化疗性腺毒性作用的敏感性，为生育力保存策略提供咨询。
