Lynch syndrome is an autosomal dominant inherited disease characterized by an elevated risk of a variety of cancers. Presently, we can expect good prognoses of colon, endometrial, and gastric cancers in patients with Lynch syndrome due to the effectiveness of surveillance for these cancers and the relatively low malignant potentials of these cancers. However, in order to increase a patient’s life expectancy, a surveillance of other Lynch syndrome-associated cancers is also necessary. Biliary tract cancer has a high incidence in the general population in eastern Asia and it is an aggressive malignancy with a poor prognosis. The biliary tract may become one of the important target organs of cancer surveillance strategies in Japan for patients with Lynch syndrome.

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Multiple endocrine neoplasia type 2 (MEN2) is autosomal dominantly inherited disease characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism. MEN2 is divided into three clinical subtypes; 2A, 2B and FMTC (familial medullary thyroid carcinoma). The causative gene for MEN2 is RET oncogene located on chromosome 10q11.2. In RET gene analysis, exons 10, 11, 13–16 should be analysed. More than 98% of MEN2 patients had RET germline mutation. RET gene testing is strongly recommended for all patients with MTC because RET mutation is discovered in approximately 10–15% of patients with apparently sporadic MTC. In Japan, RET gene testing can be performed under health insurance system since April 2016.
RET gene testing can discriminate relatives with mutation from those without mutation. So, prophylactic total thyroidectomy for children with RET mutation can be performed. The narrow definition of prophylactic total thyroidectomy is that total resection of the normal thyroid gland before the development of MTC in children. Therapeutic early total thyroidectomy for children with micro MTC or C-cell hyperplasia should be distinguished from prophylactic total thyroidectomy (narrow definition). In Japan, prophylactic total thyroidectomy (narrow definition) for children has not been performed because of the limitation of health insurance system. However, prophylactic or therapeutic early total thyroidectomy without severe complication such as recurrent laryngeal nerve palsy and permanent hypoparathyroidism should be widely accepted in Japan.

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Japanese Society for Cancer of the Colon and Rectum (JSCCR) has issued the JSCCR Guidelines 2012 for the Clinical Practice of Hereditary Colorectal Cancer for which the JSCCR Familial Colorectal Cancer Committee took the initiative in the development with the cooperation of the Japanese Society for Familial Tumors. In 2012, familial adenomatous polyposis (FAP) working group established in the JSCCR Familial Colorectal Cancer Committee has launched a retrospective multicenter cohort study. This study was designed to clarify the characteristics of the disease in the Japanese population and to disclose an actual status of the treatment of FAP in Japan which were expected to be rationales for the revision of the guidelines. This study involved 23 Japanese special institutions for colorectal diseases and clinical data were accumulated comprehensively in 303 FAP patients who underwent first surgical interventions between 2000 and 2012. These data are currently being analyzed in terms of following seven points: i.e., (1) time trend of surgical treatment; (2) risk of cancer development; (3) surgical procedure and postoperative complications; (4) risk factors of FAP-associated extra-colonic tumors and their treatment; (5) morphological analysis of colonic tumors; (6) clinical features of attenuated FAP; (7) influence of hospital characteristics on FAP treatment. Further initiatives by JSCCR should include some prospective cohort studies focusing on specific clinical questions to established EBM-based clinical practice for FAP patients in Japan.

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We herein describe the recent trends in treating Lynch syndrome (LS) over the past years conducted by the Japanese Society for Cancer of the Colon and Rectum (JSCCR) and discuss the current controversies and future prospects. The JSCCR was established in 1973. In 1991, the JSCCR proposed Japanese criteria to select patients with suspected LS and registered suspected LS families according to these criteria. From 1997 to 2010, the HNPCC registry and genetic testing project was implemented. In 2012, the JSCCR compiled the “JSCCR guidelines 2012 for the clinical practice of hereditary colorectal cancer”. Collaborations between relevant organizations are needed to manage various clinical issues in patients with LS.

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Hereditary breast and ovarian cancer (HBOC) is a familial neoplastic syndrome that frequently develops as both breast and ovarian cancer. Mutations of BRCA1 and BRCA2 genes have been identified as the cause of HBOC. Poly ADP-ribose polymerase (PARP) inhibitors have attracted attention as novel therapeutic agents for cancers with BRCA mutation. In 2014, olaparib was approved by the FDA as the first PARP inhibitor, and many clinical studies of PARP inhibitors are in progress. With "BRCAness", a homologous recombination deficiency, PARP inhibitors have also recently been shown to be effective for cancer without BRCA1/2 mutation. The HRD score has been proposed to be a useful indicator for BRCAness. These results suggest that PARP inhibitors are likely to extend the application range and efficacy of tailor-made treatment.

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