Research On Risk Factors And BRCA1/2Mutations Of Female Breast Cancer In Zhejiang Area

Breast cancer is the most common malignancy in women worldwide which poses a grave threat to women’s health, both physically and mentally. In recent years, breast cancer incidence and mortality rates have been decreasing in many western countries largely due to early detection through screening programs and improved treatment. In China, with the rapid development of the society and the economy, incidences of breast cancer are increasing. Breast cancer is quite serious in some big cities and economic developed regions, like Zhejiang Province, and it even ranks the largest percentage among women malignancies. So one question arises, namely, what factors may cause breast cancer in Zhejiang Province? Unfortunately, no comprehensive research has been done on this subject. So far as we know, about5%to10%of breast cancers are hereditary breast cancers,60%of inherited breast cancers are caused by BRCA1or BRCA2gene mutations. BRCA1or BRCA2mutation carriers are at a higher risk of suffering from breast cancer and ovarian cancer. Several studies have shown Jews have some mutational hotspots, such as185delAG and5382insC of BRCA1, and6174delT of BRCA2. Researches in recent years haven’t yet found Chinese people have such mutational hotspots. The distribution of BRCA1and BRCA2mutations in women diagnosed with breast carcinoma of Zhejiang Province is unknown.In this study, we make a thorough research on how personal factors, genetic biological factors, living behaviors are related to breast cancers in Zhejiang Province, and then carry on genetic testing for BRCA1and BRCA2mutations. In this way, risk factors and mutational characteristics of breast cancer can be further identified. So that, genetic screening guidelines and individual prevention for breast cancer can be developed.Objective:To estimate the risk factors for breast cancer and establish efficiency measurements for individual prevention, we present a1:1matched case-control study of personal factors, genetic biological factors, living behaviors and take gene testing for BRCA1/2gene mutations for breast cancer in Zhejiang Province.Methods:Subjects were women in Zhejiang Province that comprised200cases of breast cancer and200matched controls without cancers and reproductive endocrine system diseases. Informations about personal factors, genetic biological factors, living behaviors were investigated and the data was analyzed using conditional logistic regression. The objects in the gene testing study were92patients chosen from the200breast cancer patients. Genomic DNA was extracted from peripheral venous blood. PCR amplification was carried out in exon-3,8,11,12,13,24of BRCA1and exon-3,5,6,10,11,18,22,23of BRCA2. The PCR products were purified and sequenced. Then the relationship between the gene mutations and breast cancer was analyzed. Results:Univariate conditional logistic regression showed that family history of malignant tumor、breast cancer and other tumors family history、large-scale decoration、mammary hyperplasia、adverse life events、bra with steel rings、sleeping with bra、high fat and pickle intake、poor sleep were positively associated with breast cancer; whereas environmental decoration materials、long decoration time interval、 workplace、more lactation and parity、high fruits intake、sufficient sleep were inversely associated with breast cancer. Multivariate conditional logistic regression analysis showed that the risk factors would include family history of other tumors [odds ratio(OR)=1.571,95%confidence interval(CI):1.029～2.396]、mammary hyperplasia (OR=3.066,95%CI:1.834～5.126)、job-related life events (OR=4.575,95%CI:1.690～12.390)、the death of relatives (OR=2.555,95%CI:1.475～4.424)、 wearing bra at night (OR=1.902,95%CI:1.177～3.072)、high intake times of fat (OR=2.709,95%CI:1.546～4.749) and salted food (OR=2.460,95%CI:1.300-4.653). Environmental decoration materials (OR=0.517,95%CI:0.339～0.789)、workplace (OR=0.430,95%CI:0.243～0.762)、more lactation (OR=0.109,95%CI:0.013～0.896)、 enough sleep (OR=0.424,95%CI:0.205～0.880) were associatied with an decreased risk of breast cancer. Furthermore,2variants of unknown and1gene polymorphism were detected in BRCA2gene, including11missense mutation1093A>C and18415G>T occurring on exon10,13synonymous mutation1593A>G occurring on exon18, the prevalence of mutations was13%. No deleterious mutations were identified in the92breast cancer patients and no mutations were observed in BRCA1gene.Conclusion:Hereditary、psychological factors、lifestyle、environmental and dietary related factors were significantly associated with breast cancer, no mutations were detected in the BRCA1gene, the BRCA2mutations may play an important role in breast cancer of Zhejiang population, this may offer a recommended screening mode for clinical genetic testing. Comprehensive measures should taken to prevent breast cancer initiation and development.