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Effects of Altered BRCA1 and p53 on Breast Cancer Prognosis in African- American Women

机译：改变BRCa1和p53对非裔美国女性乳腺癌预后的影响

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Breast Cancer (BC) is the second leading cause of death among women in the United States. Although the incidence of breast cancer is higher in American White (AW) women, mortality in African American (AA) is considerably higher. These differences are perhaps due to histological and socioeconomic factors. Mutations of the tumor suppressor gene p53 are among the most common genetic defects in cancer cells, and in several studies alterations in p53 in breast cancer have been associated with a poor prognosis. Individual carrying mutations in p53 or inactivation of BRCAl genes are predisposed to a variety of cancers, both tumor suppressor genes have been implicated in establishing genome stability by participating in DNA damage pathways. There have been discrete p53 mutations in AA cohort, which were different WA cohorts. Mutations in BRCAl gene accounts for about 50% of inherited breast cancer cases, but somatic mutations of BRCAl gene are absent in sporadic cancers. Inactivation of BRCAl occurs via the hypermethylation of the promoter region of the BRCAl gene in sporadic cancers. We have compared the mutation of p53 gene and inactivation of BRCA1 gene in AA and AW population. We found that: (1)Higher p53 overexpression, representative of presence of mutant p53 protein, was observed in AAs then in AWs woman; (2) The number of p53 mutations were more in AA as compared to AWs; (3) Hypermethylation of promoter of BRCAl gene was seen in cases where p53 was muted irrespective of race. This study, when complete will establish a causal variation in AAs as compared to WAs.

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