Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor.

IF 2 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2022-03-21 DOI:10.1186/s13053-022-00218-0

Alicja Ogrodniczak, Janusz Menkiszak, Jacek Gronwald, Joanna Tomiczek-Szwiec, Marek Szwiec, Cezary Cybulski, Tadeusz Dębniak, Tomasz Huzarski, Aleksandra Tołoczko-Grabarek, Tomasz Byrski, Katarzyna Białkowska, Karolina Prajzendanc, Piotr Baszuk, Jan Lubiński, Anna Jakubowska

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引用次数: 2

Abstract

Background: There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs.

Methods: The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated.

Results: The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45-15.43, p=0.01).

Conclusions: Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.

查看原文本刊更多论文

BRCA1、BRCA2、RAD51C、PALB2和CHEK2复发性突变与交界性卵巢肿瘤风险的关系

背景:有几个基因与卵巢癌风险相关。交界性卵巢肿瘤(BOT)的分子变化表明这种疾病与I型卵巢肿瘤(低级别卵巢癌)有联系。本研究确定了BRCA1、BRCA2、PALB2、RAD51C和CHEK2突变的患病率及其与bot风险的关联。方法:研究组由102例经组织学证实的BOT患者和1743名健康对照者组成。并对167例G1期卵巢癌进行分析。分析包括定位于5个基因(BRCA1、BRCA2、PALB2、RAD51C和CHEK2)的21个创始和复发突变的基因分型。评估了发生BOT和低级别卵巢癌的风险，以及测试突变与生存的关系。结果:CHEK2错义突变(C . 470t >C)与BOT风险增加2倍(OR=2.05, p=0.03)、诊断年龄更早、10年生存率降低约10%相关。BRCA1和PALB2基因突变与卵巢癌G1的高风险相关(分别为OR=8.53, p=0.005和OR=7.03, p=0.03)，与BRCA1携带者全因生存率较差相关(HR=4.73, 95%CI 1.45-15.43, p=0.01)。结论:结果提示CHEK2 (C . 470t >C)可能在BOT发病机制中发挥作用，但由于BOT患者较少，所得结果应视为初步结果。需要更大规模更深入的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.