Hereditary and familial prostate cancers respectively account for about 5% and 20% of all prostate cancer in the United States. The most striking characteristic of familial prostate cancer is the early-onset of the disease. In the clinical setting, a family history of prostate cancer is recognized as a high risk for developing prostate cancer, and a risk-based prostate cancer screening program for it has been proposed. Genetic analyses for identifying the susceptible genes have been reported, and it appears that multiple genes are involved in the development of prostate cancer. Recently, genome-wide association studies showed that the single nucleotide polymorphisms located at the 8q24 region had an association with prostate cancer development. Familial prostate cancer, although its incident rate is relatively rare, must be treated as a high-risk group. Further clinical and basic research is warranted to explore the mechanism of prostate cancer development.

Since the international gastric cancer linkage consortium first proposed screening criteria for the detection of CDH1 germline mutations in hereditary diffuse gastric cancer(HDGC), the low yields of previous attempts to identify patients with HDGC in Japan, where gastric cancer is endemic and mass screenings for it have been established, have made clinicians less enthusiastic about pursuing the genetic etiology of the peculiar occurrence of gastric cancer. A report published in 2011 described a case with a typical truncated mutation of CDH1 and another with an exon 3 deletion of this gene. These findings have rekindled the curiosity of practicians and pathologists confronted with unusual gastric cancers of various types such as younger- onset, familial clustering, or the exhibition of a specific characteristic morphology. The status and history of the investigation of the genetic backgrounds of Japanese gastric cancers are reviewed, and the pathological features of the Japanese cases of HDGC are described.

Li-Fraumeni syndrome(LFS)is the autosomal-dominant familial cancer predisposition syndrome. The criteria for it have already been defined, and most patients with this syndrome have been identified with germline mutations in the p53 tumor suppressor gene(TP53). More recently, the feasibility and potential clinical effect of a comprehensive surveillance of asymptomatic TP53 mutation carriers of this syndrome are being shown. However, the prevention and treatment recommendations for cancer, and the support system for LFS, are insufficient. In the future, patients with this syndrome require more developed medical treatment because they and their families have profound medical issues and psychosocial distress.

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer, HNPCC, is a cancer-predisposing autosomal-dominant hereditary disorder caused by defects of the mismatch repair(MMR)system during DNA replication. Not only colorectal cancer, but malignancies in various organs, e.g., endometrium, stomach, small intestine, and urinary tract, occur in people of a relatively young age and accumulate in the family; therefore, this syndrome is considered to be a very important clinical entity with regard to the cancer treatment strategy. Germline mutations of 4 MMR genes, e.g., MLH1, MSH2, MSH6 and PMS2, had been identified as the cause of this disease, however, a novel mechanism, epigenetic inactivation of MSH2 gene due to hypermethylation of promotor region by the deletion of 3'part of epithelial cell adhesion molecule(EPCAM) gene which is located upstream of the MSH2 gene, has been reported in recent years. Therefore, it should be kept in mind in genetic testing and/or counseling for Lynch syndrome case with MSH2 defect that there might be a deletion of the EPCAM gene. In this review, the significance of the EPCAM gene defect in the management for Lynch syndrome is briefly introduced.

Although the progress in understanding human genetics regarding cancer has been applied to the medical practice of treating hereditary cancers in developed western countries, it is not widely implemented in Japan. We started treating hereditary cancers at NHO Shikoku Cancer Center in November 2000. Our institution has a multidisciplinary team that provides medical care and genetic counseling for patients with hereditary cancers, and their relatives. The team consists of doctors from several related departments, and paramedics including a genetic counselor who participated as of 2009. Medical care of patients with hereditary cancers should not be separated from general oncological practice, but incorporate all medical professionals, including doctors of related departments and paramedic. We have attempted to identify patients with hereditary cancer and their family members and relatives at high risk; we followed them up and provided risk-reducing therapies for them at our cancer center. Here we present the framework of our practice in treating hereditary cancers. We discuss appropriate goals and future perspectives in the field of hereditary cancer in Japan.