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BRCA1/2 致病性变异携带者行输卵管卵巢切除术降低风险后发生浆液性子宫内膜癌的风险。

Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy.

机构信息

Department of Genetics, Institut Curie, Paris, France; Department of Pathology and Department of Breast and Gynecological Surgery, Institut Curie, René Huguenin Hospital, Saint-Cloud, France; Université Versailles-St-Quentin-en-Yvelines, EA 7285, Saint-Quentin, France; Institut Curie, INSERM U830, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

出版信息

J Natl Cancer Inst. 2018 Feb 1;110(2). doi: 10.1093/jnci/djx159.

Abstract

It has recently been shown that the risk of a rare subtype of endometrial carcinoma (serous type) in women carrying a germline BRCA1/2 pathogenic variant is increased. We assessed the incidence of serous endometrial carcinoma in an independent prospective cohort study of 369 BRCA1/2 women (1779 woman-years of follow-up) who underwent risk-reducing salpingo-oophorectomy by laparoscopy. This occurrence in two BRCA1 carriers led us to estimate that BRCA1/2 carriers present a higher risk than the control population (standardized incidence ratio = 32.2, 95% confidence interval = 11.5 to 116.4, P < .001, two-sided chi-square test, 1 degree of freedom). In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis. Prophylactic hysterectomy could be discussed with informed women through a shared decision-making process although the estimated 3% life-long risk is moderate. Additional studies are required to establish future prophylactic surgery guidelines.

摘要

最近有研究表明,携带种系 BRCA1/2 致病性变异的女性中罕见的子宫内膜癌(浆液型)风险增加。我们评估了 369 名接受腹腔镜下预防性输卵管卵巢切除术的 BRCA1/2 女性(1779 名女性年随访)的独立前瞻性队列研究中浆液性子宫内膜癌的发生率。这两例 BRCA1 携带者的发生使我们估计 BRCA1/2 携带者的风险高于对照人群(标准化发病比=32.2,95%置信区间=11.5 至 116.4,P<.001,双侧卡方检验,自由度为 1)。此外,在这两个肿瘤中,野生型 BRCA1 等位基因丢失,表明 BRCA1 基因失活,与子宫内膜癌发生有关。可以通过共同决策过程与知情女性讨论预防性子宫切除术,尽管估计终生风险为 3% 是中度的。需要进一步的研究来制定未来的预防性手术指南。

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