The Analysis Of CHEK2 Gene Mutation And The Clinical Retrospective Study On Familial Breast Cancer

Part I The analysis of CHEK2 gene mutation in breast cancer familiesObjective: The aim of the study was to explore the prevalence, the "hot spots" of CHEK2, and whether Chinese breast cancer families with BRCA1 mutation excluded had characteristic mutation of CHEK2 in contrast to the western breast cancer families.Methods: 33 breast cancer families, including 76 breast cancer patients and 42 relatives, and 8 normal women as a control were recruited. 76 breast cancer patients were admitted in Tianjin Cancer Hospital between October 2003 to December 2005, and were diagnosed by pathology. The control group was considered to be healthy individual with breast cancer, ovarian cancer and other tumor excluded. Peripheral blood mononuclear cells were collected to obtain genomic DNA by blood DNA kit. All participants had written informed consent. The mutation of CHEK2 was detected by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP). Then, the doubted samples were sent to DNA sequencing. Results: 6 breast cancer patients were founded with CHEK2 mutation, accounted for5.2%(6/116) of all family participants and 6.8%(6/74) of familial breast cancer patients. 6 breast cancer patients belonged to 4 breast cancer families that three of 4 breast cancer families with mutation were families that diagnosed at any age, with >2 close blood relatives with breast cancer;and one was the family that diagnosed at age <30yr, with >1 close blood relatives with breast cancer. No mutation was occurred in relatives and the control group. 8 mutation types were founded. Four of them were deletion mutation, and four were missense mutation, which leaded to the change of single amino acids. In addition, 50489delT was detected in two breast cancer patients.Conclusion: The prevalence of CHEK2 mutation in breast cancer families in Tianjin is similar to that observed in western country. Whether 50489delT is the "hot spot" of CHEK2 mutation in Chinese breast cancer families waits on further research.Part II The clinical retrospective study on familial breast cancerObjective: To explore the clinical features and prognosis of breast cancer patients with positive family history.Methods: Data collected from 1999 breast cancer patients admitted in Tianiin Cancer Hospital between August 1st 1989 and June 30th 1994 were analyzed retrospectively, including Group FHP: 87 breast cancer patients with family historypositive(FHP) and Group FHN: 1912 breast cancer patients with family historynegative(FHN). Clinical data of two groups were compared.Results: Clinical stage in Group FHP was significantly earlier than that of GroupFHN(x2=7.206, P=0.027), and the incidence rate of metastasis of lymph node inGroup FHP(37.2%) was significantly lower than that of Group FHN(50.2%), x2=5.585, P=0.018. However, the difference had no statistical significance in age,menopause status, tumor size, pathologic type, estrogen receptors(ER) orprogestogen receptors(PR) status, local recurrence and systematic metastasis 3 yearsafter operation(respectively, *'=2.088, 1.290, 1.653, 2.202, 0.270, 0.026,1.804;andseparately, P=0.554, 0.256, 0.438, 0.532, 0.603, 0.872, 0.179). Overall 5-year and10-year survival rate in Group FHP(89.63%;79.12%), as compared with those ofGroup FHN(81.53%;73.77%), no statistical significance existed between bothgroups(Log Rank= 1.260, i>=0.262).Conclusion: The study did not find that positive family history is statisticallyassociated with clinical prognosis;and our finding suggests that FHP patients wouldbe obtained efficiency similar to FHN patients, if prompt measure had been taken.Further research is needed to verify this finding.