The Analysis Of BRCA1 Mutations In 41 Chinese Patients With Early Onset Breast Cancer And Affected Relatives

Breast cancer is one of the most common malignant tumors which seriously threaten the health of women. In shanghai, breast cancer is the most frequent cancer among women. A large part of breast cancer is early onset or familiar and 20~25% breast cancer patients have family history. BRCA1 gene was isolated in the middle '90s (Miki et al., 1994), and carriers of germ-line mutations in this gene are at increased risk of developing breast cacner. The incidence of BRCA1 gene mutations is high in the early onset and familiar breast cancer patients.To study the BRCA1 gene mutation and the clinical and pathological features of Chinese mutation carriers, we detected the BRCA1 gene mutation in Chinese early onset and familiar breast cancer patients and we also compared the mutation associated breast cancer to the sporadic one in pathological and mammographic features.1. The BRCA1 gene mutation detection and analysis in Chinese patients with early onset breast cancer and affected relatives.To study the BRCA1 mutations in eastern Chinese patients with early onset breast cancer and affected relatives, 41 patients' genomic DNA from peripheral mononuclear blood cells was studied by using single strand conformational polymorphism (SSCP) and DNA sequencing. The BRCA1 mutations were detected in the whole gene sequence. Three novel disease-causing mutations (c.582 C>T, c.735 C>T and c.2790delT) occurred in all the patients. Two occurred in the patients younger than 35 years old (9.1%) and one in the patients with affected relatives (5%). Additional sequence variants identified included a novel mis-sense mutation of unknown significance and six polymorphisms. The prevalence of BRCA1 mutations in Chinese patients in Shanghai with early onset breast cancer is similar to that observed in western women, but the incidence of mutations in breast cancer patientsin Shanghai with affected relatives isn't as high as that in western women. No founder mutations were found in Chinese breast cancer patients.2. The descriptive study of the pathological and immunohistochemical features of Chinese BRCA1 mutation associated breast cancer.In this section, we studied 3 cases BRCA1 mutation associated breast cancer patients'(from the first section) pathological and immunohistochemical features. We chose all the breast cancer patients who received treatment in our department from Oct. 2000 to Sep. 2001 as the controls. Comparing to the sporadic breast cancer, the mutation associated breast cancer was poor differentiation and had high grade in tumor cells. ER, PR and c-erbB-2 were less frequently expressed and p53 was more frequently expressed in tumors of BRCA1 carriers than the controls. The results implied Chinese BRCA1 associated breast cancer maybe had similar pathological and immunohistochemical features as western patients. But we still needed more patients to perform the statistical analysis and confirm the result of our study.3. The descriptive study of the mammographic features of Chinese BRCA1 mutation associated breast cancer.To compare the mammographic features of the Chinese breast cancer patients who carry BRCA1 mutations and sporadic breast cancer patients. 3 cases of breast cancer patients who carry BRCA1 mutations and 9 cases of sporadic breast cancer patients were matched according to age and year of diagnosis. The mammograms of these 12 patients were reviewed by an experienced radiologist on tumor appearance and breast density. Mammography was more frequently false-negative in carriers than controls (66.7% vs. 11.1%), and the mean density score of normal breast tissue in carriers group is higher than the controls (3.7 vs 2.7). But we still needed more patients to perform the statistical analysis and confirm the result of our study.This is one of the earliest systematic studies on BRCA1 mutations among patients inhabited in Eastern China with early onset breast cancer and affected relatives. It still leaves room for a further study.