Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Gynecol Oncol. 2023 Sep;34(5):e66. doi: 10.3802/jgo.2023.34.e66. Epub 2023 May 2.
Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers.
Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing.
We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). and were the most dominant genes associated with hereditary breast and ovarian cancer, whereas was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories.
The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.
遗传高危评估将乳腺癌、卵巢癌和胰腺癌合并为一种综合征。然而，目前缺乏比较这三种癌症中易患癌症相关基因的种系突变谱的数据。
符合遗传性乳腺癌、卵巢癌和胰腺癌标准的患者入组并接受多基因测序。
我们共入组了 730 名先证者：418 名患有乳腺癌，185 名患有卵巢癌，145 名患有胰腺癌。在 18 名患有两种癌症的患者中，16 名患有乳腺癌和卵巢癌，2 名患有乳腺癌和胰腺癌。共有 167 名（22.9%）患者携带 170 种突变。乳腺癌、卵巢癌和胰腺癌的突变频率分别为 22.3%、33.5%和 17.2%。双癌患者的突变率明显高于单癌患者（p<0.001）。和 是与遗传性乳腺癌和卵巢癌最相关的主要基因，而 是与遗传性胰腺癌最相关的基因。遗传性结肠癌基因如林奇综合征在部分胰腺癌或卵巢癌患者中存在，但在乳腺癌患者中很少见。既有卵巢癌又有乳腺癌家族史的家庭的突变率高于其他家族史的家庭。
突变谱在三种癌症类型和家族史中存在差异。我们的分析为医生、咨询师和咨询对象提供了关于遗传咨询的提供和接受的指导。
