The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) I n Japan, breast cancer is the most frequent malignancy in women and estimates of new cases and deaths in 2002 were 32 245 and 9178, respectively.(1) The standardized incidence ratio of breast cancer in Japan was approximately one-third that of the US (32.7 vs 101.7 per 100 000 women).(1) The incidence of breast cancer in Japanese women shows a steady increase; however, it is still much lower than in Western countries. In breast cancer, family history is the strongest risk factor for cancer predisposition. Epidemiological studies showed that 12% of women with breast cancer have one affected family member and 1% have two or more affected relatives.(2) Women with one, two, and three or more first-degree affected relatives have an increased breast cancer risk when compared with women who do not have an affected relative (risk ratios 1.8, 2.9, and 3.9, respectively).(2) Recent advances in molecular genetics elucidated BRCA1 and BRCA2 (BRCA1/2) as two major susceptibility genes for breast cancer predisposition.(3,4) Gene testing of BRCA1/2 is available as a routine clinical test for diagnosing hereditary breast/ovarian cancer (HBOC) in the US and other Western countries, (5,6) while only a few reports have been published concerning the prevalence of BRCA1/2 mutations among Japanese people. (7)(8)(9)(10)(11)(12) The methods of genetic analysis employed in these studies varied, such as polymerase chain reaction (PCR)/ single strand conformational polymorphisms (SSCP), protein truncation test, and PCR/direct sequencing, but they were performed as preliminary in-house tests in the research setting. In the US, commercial BRCA1/2 gene testing was initiated by M...

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BackgroundThere are no definitive criteria for identifying which patients with The International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer will benefit from adjuvant therapy after radical hysterectomy. The aims of this study were to clarify the efficacy of adjuvant therapy and assess complications after radical hysterectomy in patients with FIGO stage IB1 cervical cancer with intermediate risk factors.MethodsBetween January 2005 and December 2009, the medical records of 75 stage IB1 patients’ intermediate risk factors (i.e., tumor size 2–4 cm, lymphovascular involvement, and/or deep stromal invasion >1/2) who underwent radical hysterectomy at six institutions were collected, and these patients were enrolled in this nonrandomized retrospective study. We simplified the criteria of intermediate risk factors as much as possible, as the criteria adopted in some clinical studies are complicated in practice.ResultsThe patients were grouped according to the receipt of adjuvant therapy as follows: 46 patients, no further treatment; 19 patients, external beam radiation treatment, including 9 patients who received brachytherapy; 5 patients, concurrent chemoradiotherapy (CCRT); and 5 patients, chemotherapy (CT). The clinical outcomes and complications in each group were analyzed. After an average follow-up of 82.6 months (range, 24–135 months), only one patient with all three risk factors who received radiotherapy (RT) experienced recurrence. Excluding this patient, the remaining patients who received RT, CCRT, or CT had two or three risk factors. Lymphedema was significantly more common among patients who received RT or CCRT, whereas the incidence of ileus and ureteral obstruction was not different among the treatment groups. However, an unsutured peritoneum increased the risk of ileus.ConclusionsThe findings of this study suggest that RT and CCRT after radical hysterectomy are not beneficial in patients with intermediate risk factors. In particular, RT and CCRT appeared to increase the incidence of lymphedema. A prospective randomized study is needed to verify the findings of this study.