Genetic testing for BRCA1/2 is conducted under insurance coverage based on specific criteria; however, reports on the detection rates of pathological variants by these criteria are lacking. This study conducted a retrospective analysis of detection rates according to the criteria. The subjects were 177 individuals referred to our hospital's clinical genetics department between April 2020 and January 2022, of whom 153 underwent testing. Pathogenic variants were detected in 15 individuals (9.8%). Notably, the detection rate was higher among patients meeting multiple criteria, with 12 out of the 67 individuals (19.7%) being identified. When only the condition of having a family history of breast cancer was considered, none of the 36 patients were detected with pathogenic variants, but detection rates increased when other conditions were also satisfied. 　From this study, it is suggested that meeting multiple criteria increases the detection rate. Additionally, although having a family history of breast cancer alone is associated with a low prior probability, checking how many other insurance eligibility criteria are met allows risk assessment to be personalized for clients, which will lead to self-determination support during genetic counseling.

　Young-onset colorectal cancer is on the increase in western countries, and there is concern that the number will increase in Japan as well. We investigated the heritability and clinicopathologic characteristics of 22 cases of young-onset colorectal cancer who were younger than 40 years old at the time of surgery among 981 cases of colorectal cancer whose primary tumor was resected between January 2011 and December 2022 at our hospital. Excluding the 2 patients with unknown family history, seven (35%) of the 20 patients had a family history of colorectal cancer in the second degree of consanguinity. The presumed causative disease was inflammatory bowel disease in 2 cases (9.1%) and genetic disease in 5 cases (22.7%). The genetic disease included two cases of familial colorectal adenomatosis, two cases of Lynch syndrome, and one case of Li-Fraumeni syndrome. Compared to control, there was no difference in stage, but the undifferentiated type was more common in young-onset colorectal cancer. Genetic testing was performed in only one LS case and led to a definite diagnosis. Young-onset colorectal cancer patients did not differ from the control group near the median in 5-year overall survival and cancer specific survival.

　Multiple Primary malignancies are defined as two or more independent cancers occuring in the same person simultaneously or metachronously. The number of reports is increasing, but remain rare. Here we report a case of 5 MPMs: during the postoperative observation period of double cancers (endometrial and ovarian), three more cancers developed in the kidney, in the colorectal and in the breast. The case was a 75y/o woman. At the age of 64, she was diagnosed with endometrial cancer and underwent surgery. Postoperative pathological examination then revealed double cancers of endometrial and ovarian cancers. She was diagnosed with renal, colon and breast cancer around 5, 7 and 8 years after the first operation. Immunohistochemistry (IHC) of mismatch repair (MMR) proteins was examined as supportive diagnosis of Lynch syndrome, but no loss of expression was observed. According to the Hereditary breast–ovarian cancer syndrome (Hereditary Breast and Ovarian cancer: HBOC) diagnostic criteria, germline BRCA1/2 gene test was performed but no pathogenic variant was detected. Patients with MPMs have a high rate of detecting pathological mutations in hereditary tumor genes. Clinical genetic specialist might play a key role for the management of those patients.

　Lynch syndrome is the most common hereditary colorectal cancer, but it often lacks clinical features and can be overlooked in routine clinical practice. This report describes a case of a 65-year-old woman who was diagnosed with Lynch syndrome following the development of metachronous multiple cancers. The patient underwent surgery for ascending colon cancer at age 42 and transverse colon cancer at age 55, with no postoperative metastasis or recurrence. At age 62, PET-CT indicated enlargement of lymph nodes at the hepatic hilum, and an unknown primary cancer (suspected pancreatic origin) was treated with gemcitabine + nab-paclitaxel. After tumor markers rose again, MSI testing revealed MSI-high, and pembrolizumab treatment led to a complete response. Subsequently, she presented with gross hematuria and was diagnosed with bladder cancer, which also showed MSI-high. The detailed family history and genetic testing revealed a pathogenic variant in MLH1, leading to a diagnosis of Lynch syndrome.

　The patient was a 28-year-old woman who was diagnosed with breast cancer after noticing a mass in her left breast. She was diagnosed with hormone receptor (HR) negative, HER2 positive, invasive ductal carcinoma (IDC) of the breast, cT2N0M0, clinical Stage ⅡA. Genetic testing revealed a pathogenic variant of the TP53 gene, confirming LFS. Following neoadjuvant chemotherapy, she underwent a left skin-sparing mastectomy and a right risk-reducing mastectomy (RRM) based on her preference. The surgical pathology results showed a pathologic complete response in the left breast, while two occult cancers were found in the prophylactic right breast specimen. She completed postoperative anti-HER2 therapy and continues with LFS surveillance. This is the first reported case in Japan in which RRM was performed on a patient with LFS as far as we investigated. Furthermore, this case is significant as it identified two occult cancers in the risk-reduced resected breast, underscoring the importance of RRM. LFS should always be considered when evaluating patients with young-onset breast cancer.

　The medical records of patients with cancer who underwent comprehensive genomic profile (CGP) testing and relatives of patients with hereditary tumors between January 2020 and February 2023, totaling 238 patients (98 women and 140 men), were reviewed. Using tissue-only sequencing and paired tissue-normal sequencing, 204 and 34 cancers were tested, respectively. Six patients were diagnosed with hereditary tumors before the CGP testing. The germline findings of paired tissue-normal sequencing or confirmatory germline testing after tissue-only sequencing identified four patients with pathogenic variants. In total, 10 patients had hereditary tumors. A total of 17/213 patients (8.0%) with sporadic tumors and 2/10 patients (20%) with hereditary tumors received CGP-based treatment (p = 0.21). Among the relatives of the patients with hereditary tumors diagnosed after the CGP testing, five relatives from two families received germline testing; three of them had BRCA2 pathogenic variants.