The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables followup analysis in Japan.

Germline MUTYH mutations were investigated in 14 Japanese colorectal polyposis patients without germ line adenomatous polyposis coli (APC) gene mutations. Three patients had a heterozygous IVS10-2A>G MUTYH mutation. The onset of MUTYH-associated polyposis (MAP) occurs later than that of familial adenomatous polyposis with germline APC mutation. Thus, we compared the carrier frequency of MUTYH IVS10-2A>G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment. The frequency of IVS10-2A>G heterozygote in APC germline mutation negative polyposis patients was significantly higher than control subject (p = 0.012, Chi square test). Although the sample size is still too small to conclude, the IVS10-2A>G MUTYH heterozygote might add to the risk of developing germline APC mutation negative polyposis.

Objective: This study investigated the psychosocial aspects of risk-reducing salpingo-oophorectomy in Japan. Methods: The subjects were 16 patients who underwent risk-reducing salpingo-oophorectomy at the Cancer Institute Hospital. Worry about cancer, emotional state and cancer-specific distress level were evaluated using a four-point Likert scale, the Profile of Mood States-Short Form and the Impact of Event Scale-Revised, respectively, before and 1 year after the surgery. In addition, the subjects were interviewed regarding their expectation for the risk-reducing surgery, the effects of the surgery, and the recovery from surgery, before the surgery and at 1, 6 and 12 months after the surgery. A t-test or Wilcoxon rank-sum test was used for the analysis, and literal analects were prepared for the interview and the answers were organized per question item using NVIVO10. Results: The results revealed that the total score for worry about breast cancer and ovarian cancer (P = 0.021) as well as the Impact of Event Scale-Revised (P = 0.021) were significantly lower 1 year after surgery, compared with the values before the surgery. Regarding the preoperative expectations for the surgery, the expectation for reducing the cancer risk was the highest. The reported effects of risk-reducing salpingo-oophorectomy on life included the appearance of menopausal symptoms, a loss of motivation and poor concentration; more effects were reported at 1 year after surgery than at 6 months after surgery. Conclusions: These results suggest that risk-reducing salpingo-oophorectomy can be effective for reducing worry about breast cancer and ovarian cancer and cancer-specific distress as well as contributing to a reduction in mortality from fallopian tube and ovarian related cancer.

Background and Aim: Gastric neoplasms (GN), including gastric adenoma and carcinoma, are well known as extracolonic manifestations of familial adenomatous polyposis (FAP). We aimed to investigate the clinicopathological features of GN in FAP patients and to clarify their relationship with the endoscopic status of the background mucosa. Methods:We analyzed the records of 39 patients who were diagnosed with FAP and underwent esophagogastroduodenoscopy between April 2005 and July 2016. Patients were divided into two groups according to atrophic gastritis (AG) status. Endoscopic findings of GN and background mucosa, and histopathological findings, including phenotypic expression of GN and mutation locus of adenomatous polyposis coli (APC) gene, were evaluated.Results: Gastric neoplasms were more predominant in the AG-positive group than in the AG-negative group (6/9, 66.7% vs 7/30, 23.3%; P = 0.039). Of 36 GN detected in 13 patients, six GN in five patients were followed and 30 GN in eight patients were endoscopically resected and analyzed. GN in the AGnegative group frequently showed whitish color, were located in the proximal stomach, and presented the gastric immunophenotype compared to GN in the AG-positive group. All GN were intramucosal lesions and were curatively resected regardless of AG status. APC germline mutations were identified in 32 patients. In patients with GN, a significantly higher number of mutation loci were among exons 10-15 (codons 564-1465).Conclusion: Clinicopathological characteristics and phenotypic expressions of GN in FAP patients depend on background mucosa status with or without AG. These findings are useful for detecting GN in FAP patients.