SY-6-1 - What should we do for better management of hereditary tumor syndromes? In the case of hereditary endocrine tumors

Abstract

About 5-10％ of cancers are thought to be hereditary of which a single gene mutation is responsible for cancer development. Hereditary cancers often show different clinical courses from those of sporadic cancers. Accordingly, different clinical management can be chosen for hereditary- and sporadic cancers. Appropriate diagnosis of hereditary cancer is thus important as it enables to offer patients better and personalized management of their cancers. Also, it enables identify at-risk family members and if they have the same genetic defect as the proband, early intervention including early, and specialized surveillance and prophylactic treatment for some tumors. There are a number of hereditary endocrine tumor syndromes such as multiple endocrine neoplasia type 1 (MEN1), MEN2, von-Hippel Lindau disease, and hyperparathyroidism-jaw tumor syndrome, which manifest various endocrine- and non-endocrine tumors. Besides these, non-syndromic hereditary single tumor such as hereditary paraganglioma-pheochromocytoma syndrome, familial isolated hyperparathyroidism and familial isolated pituitary adenoma are also known. These syndromes based on the pathological germline mutation of the responsible gene and the mutation can be transmitted to the offspring. In the case of MEN2, nearly all patients develop medullary thyroid carcinoma (MTC) as early as in childhood, As about 30% of patients with MTC have MEN2 as their genetic background, all patients with MTC is strongly recommended to have genetic testing for MEN2 (RET mutation analysis). Once pathological germline mutation is detected, surgical procedure for MTC, surveillance for pheochromocytoma, and presymptomatic genetic testing for at-risk relatives are considered. In 2016, RET mutation analysis was added to the list of insurance-covered genetic testing in Japan. This will facilitate to perform testing at clinical practice which will reduce proportion of undiagnosed patients, while it could cause some complex problems related genetic counseling and family matters. All clinicians should be aware the power and impact of genetic information on clinical management and that on patients and family members.