Breast Cancer Gene (BRCA1, BRCA2)
Authors: Lee Chang Hyun 
Published: May 2022

Most women with breast cancer do not have a familial history of the disease in a first degree relative and hereditary breast cancer caused by a mutant gene passed from parents to their children is rare; only 5-10% of breast cancers are estimated to be attributable to the inheritance of rare highly penetrant, germline mutations of genes, although this proportion is at younger ages of diagnosis. Mutations in BRCA1 and BRCA2 are responsible for most of these inherited breast cancers. Hereditary predisposition to breast cancer is responsible for autosomal-dominant transmission. Children of parents with a BRCA1 or BRCA2 mutation have a 50% chance of inheriting gene mutation. Hereditary breast cancer is characterized by early age at onset than sporadic cases, bilaterality, vertical transmission through both maternal and paternal lines, and familial association with tumors of other organs, particularly the ovary and prostate gland. Of the several hundred mutations in these genes, most lead to a frameshift resulting in missing or nonfunctioning proteins. Most of the BRCA1 an BRCA2 mutations are predicted to produce a truncated protein product, supporting the hypothesis that they are tumor suppressor genes. Progress in determining the function of BRCA1 an BRCA2 suggests that they are involved in two fundamental cellular processes, DNA damage repair and transcriptional regulation. The assessments of familial cancer risk are extremely varied, including families from different ethnic backgrounds with greater or less numbers of affective relatives at varying ages. And estimates of penetrance for BRCA1 and BRCA2 mutations range from 36% to 85% for breast cancer, and 16% to 60% for ovarian cancer. Tliree specific mutations in these genes accounted for 90% of the BRCA1 and BRCA2 variants within Ashkenazi Jewish population. For molecular correlations, BRCA1 cancers were shown to be more often estrogen receptor negative, more high grade tumors and more frequent mutations in p53 than nonhereditary cancers. The risk for breast cancer in female BRCA2 mutation earners appeal's similar to that for BRCA1 carriers, but the age of onset is shifted to an older age distribution. The growing body of data elucidating the functions of these genes suggest a gatekeeper role, characterized by interactions with other genes in the regulations of the cell cycle and DNA repair and may provide novel opportunities to develop genotype-based therapeutic approaches to treatment and prevention. Surveillance recommendations for women with germline BRCA mutations are necessary and women are encouraged to leam and practice breast self-examination beginning at age 18 and to begin annual mammogram screening at age 25. A number of women with BRCA mutations may consider undergoing surgical procedures (mastectomy and salpingooophorectomy) in attempt to reduce their risk. Nonsurgical options (tamoxifen medication) tor the prevention of hereditary breast cancer are currently limited.The choice of whether to undergo genetic testing is difficult on and should be made only after extensive consultation with a professional who is well versed in the counseling and management of families at hereditary risk. And psychological consequences of testing and the potential impact on family dynamics ai*e important considerations that must be individually addressed.The identification and location of these breast cancer genes will now permit further investigation of the precise role they play in cancer progression and will allow us to determine the percentage of total breast cancer caused by the inheritance of mutant genes. This in turn will ultimately enrich our understanding of all breast cancer, sporadic as well as hereditary, and will facilitate the identification of high-risk individuals. Most of above mentioned data are based on studies of European ancestry. It is needed to study many aspects of Korean breast cancer including age specific mutation prevalence, penetrance, molecular correlation, pathology, prognosis, surveillance and prevention options for women with BRCA mutations.In genetic studies, we need to examine the psychological and clinical impact of using gene-based diagnostic tests in families with heritable forms of breast cancer, assess public knowledge and attitudes about genetic testing for cancer risks and gather information needed to establish clinical protocols for the optimum use of these risk assessment technologies in the future.Furthermore, at least half of hereditary breast cancers are not linked to these genes. Remaining cases are not caused by another single, unidentified gene, but rather by many genes, each accounting for a small fraction of breast cancers.