[Clinical aspects of familial ovarian cancer - current status and issues in Japan].

Abstract Familial ovarian cancer occurs as part of two genetically distinct syndromes: hereditary breast and ovarian cancer (HBOC) and hereditary nonpolyposis colorectal cancer (HNPCC). HBOC caused by inherited mutations of BRCA1/2 and HNPCC caused by mismatch-repair genes are considered responsible for about 65 to 75% and 10 to 15% of familial ovarian cancers, respectively. Germline mutations of BRCA1 are considered responsible for about 50% of ovarian cancer families and 80% of breast-ovarian cancer families. BRCA2 mutations are less common than BRCA1 mutations in ovarian cancer families. A high proportion of serous adenocarcinomas at an advanced stage has been reported with BRCA-related ovarian cancers in several studies. It is controversial whether BRCA-related ovarian cancer patients carry a better prognosis despite the aggressive tumor-pathological characteristics of their disease, compared to sporadic cases. However, a good therapeutic response may be attributable to platinum-based chemotherapy. Recently in Japan, gene testing of BRCA1/2 has been available as a routine clinical test for diagnosing ovarian cancer families. Because the mutation spectrum of BRCA1/2 in Japanese was different from that of non-Ashkenazi individuals, the clinical application of BRCA1/2 gene testing for Japanese has been advocated. Approximately 1-5% of ovarian cancer patients in Japan are thought to have a family history of breast and/or ovarian cancer. The prevalence of deleterious mutations of BRCA1/2 in Japanese was reportedly significantly higher than that of non-Ashkenazi individuals despite the low frequency of familial cases in Japan. Although the age at diagnosis of ovarian cancers with BRCA1/2 mutation in the United States was earlier than those of the sporadic cases, there were no differences among Japanese. These results suggest that clinical and genetic aspects of BRCA-related ovarian cancer of the Japanese are different from those of Caucasians. A serious issue in this field is how the results will lead to a basis for the clinical application of a cancer prevention strategy targeting BRCA mutation carriers in Japanese.