We conducted a preventive surgery to reduce cancer risk for 2 cases with an identical BRCA1 gene mutation (NM_007294.3: c.3397_3398delTT). Both cases were 42 years old at the time of the preventive surgery, performed after repeated genetic counseling in consideration of childbirth hope and age to give birth. There was no occult cancer pathologically in either case, and both are still under surveillance and no evidence for the onset of cancer. In this study, we focus on the contents of genetic counseling conducted for the cases.
Clinical features of the hereditary gastrointestinal cancer syndrome overlap each other to some extent, and thus it is sometimes difficult to provide a definite diagnosis solely based on the clinico-pathological factors and family cancer history. In order to solve this big-issue, we established a Study Group for Establishment of Diagnosis of Hereditary Gastrointestinal Tract Cancer Syndromes Based on a Next-Generation Sequencing Technology (SGHGCS) in 2013. We briefly summarize our research activities thus far in accordance with the related ones of domestic and international. In 2019, the era of cancer-genome medicine comes finally true here in Japan. Numbers of problems to be solved about this are assumed. A possible establishment of a collaborative relationship among various study groups relative to the familial cancer may provide a clue to cope with these important matters.
Our study group consists of more than 40 participants / collaborators including experts in pediatric oncology, cancer predisposition, and guideline preparation, genetic counselor, ethicologists, epidemiologists, and member of the Children’s Cancer Association of Japan. The object is to construct medical system based on precision genetics for patients with pediatric cancer predispositions, and the tasks are to prepare guidelines on medical care and genetic counselling for pediatric cancer predispositions, especially Li-Fraumeni syndrome. Guidelines of medical care and genetic counselling will be developed based on detailed evidences obtained by systematic review of relevant literatures. Furthermore, we will publish summaries of the recommended surveillance systems for pediatric cancer predispositions, which was formulated in the Childhood Cancer Predispositon Workshop of the American Association for Cancer Research in 2016 and published in the journal Clinical Cancer Research in 2017.
Birt-Hogg-Dubé (BHD) syndrome is a genetic disorder characterized by cutaneous fibrofolliculomas, lung cysts and kidney cancers. Affected individuals inherit germline mutations in the folliculin gene （FLCN）, which was identified by Nickerson et al. in 2002. Most individuals have multiple bilateral lung cysts. On the other hand, Japanese patients present with inconspicuous papules that do not lead them to a dermatologist. One third of individuals over 40 years of age develops kidney cancer. Since pathogenic FLCN variants are detectable by sanger sequencing analysis in around 90% of affected family members, definitive diagnosis of BHD syndrome is usually confirmed with genetic testing. We BHD-NET （http://www.bhd-net.jp/） update the latest information of the disease, respond to consultation by physicians, and support the affected families through exchange meetings.
Multiple endocrine neoplasia (MEN) is a hereditary tumor syndrome with a development of tumors in multiple endocrine organs and is clinically divided into MEN1 and MEN2. MEN1 is autosomal dominantly inherited syndrome characterized by primary hyperparathyroidism (parathyroid hyperplasia), pancreatic gastroduodenal neuroendocrine tumor, pituitary tumor, adrenal cortical hyperplasia, and thymic neuroendocrine tumor. The causative gene for this syndrome is MEN1 gene located on chromosome 11q13. MEN2 is also autosomal dominantly inherited syndrome characterized by medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism (parathyroid hyperplasia). The causative gene for MEN2 is RET gene located on chromosome 10q11.2. Both syndromes are rare diseases with the occurrence rate being only about between 1/30,000 and 1/40,000 peoples, and the details of the disease characteristics in Japanese patients had not been well known. Therefore, we established MEN consortium Japan in 2008. The aims of activities in MEN consortium Japan are the construction of database, current situation survey for Japanese MEN patients, the construction of clinical guideline, improvement of diagnosis and treatment, support for MEN patients and families, and educational activities. The achievements of this consorsium are the collection and analysis of clinical data of MEN patients, the construction of diagnostic flowchart, the construction of degree of severity of the disease, accession of genetic diagnosis of the MEN1 and RET genes, the promotion of genetic diagnosis to advanced medical technology and insurance listing, the spread of information of the diseases by consortium’s home page, the publication of clinical guide book, the publication of patient’s book for MEN, the support for patient’s association, held of public open lectures all over Japan. To continue these activities, it is necessary to maintain not only the network for doctors performing a medical care for MEN, but also the economic base.
Along with the recent development of analytical techniques, human omics data derived from various research has been explosively increased, however there was no public repository for sharing individual data in Japan. National BioScience Database Center (NBDC), JST developed and started operation of "NBDC Human Database" (https://humandbs.
biosciencedbc.jp/) since October 2013. In addition, NBDC also developed NBDC's integrated database of Japanese genomic variation "TogoVar" (https://
togovar.biosciencedbc.jp/) in collaboration with the Database Center for Life Science (DBCLS), ROIS-DS and made it public in June, 2018. “TogoVar” enables one-stop search among the variant variation data in Japanese population derived from 180,000 genomic data of "NBDC Human Database", the variant data from other domestic and foreign projects and information regarding interpretation of variants from various domestic and foreign databases.
This paper introduces the outline of these web services.