Mutations breast cancer

A U.S. study found no association between overall breast cancer and current or past OC use. Although some studies have found differences in risk of breast cancer based on the presence of BRCA1 and BRCA2 mutations, the most recent cohort study found no association with low-dose OCs and the presence of either mutation. 

The choice to use CHCs should not be affected by the presence of benign breast disease or a family history of breast cancer with either mutation. The WHO precautions state that women with recent personal history of breast cancer should not use CHCs, but that CHCs can be considered in women without evidence of disease for 5 years. 

Based on this concept of correlation between high replication rate/high persistent mutation risk, Pike et al. (1983) formulated the hypothesis of breast tissue age and developed a mathematical model to predict the effects of exposure to ovarian hormones. This model incorporates reproductive and endocrine items related to breast cancer and is able to predict the relative risk of individual situations with results that are very close to those observed in clinical trials. According to this hypothesis, both the years of exposure and the circulating serum levels of estrogens are associated to short-term breast cancer risk in postmenopausal women (Toniolo et al. 1995). 

King, M.C., et al., "Tamoxifen and Breast Cancer Incidence Among Women with Inherited Mutations in BRCA1 and BRCA2," JAMA, 286, 2251-2256 (2001). 

Altmannsberger M, Dirk T, Droese M, Weber K, Osborn M (1986) Keratin polypeptide distribu tion in benign and malignant breast tumors subdivision of ductal carcinomas using monoclo nal antibodies. Virchows Arch B Cell Pathol Incl Mol Pathol 51(3) 265 275 Assefnia S, Jones LP, Torre KM, Furth PA (2006) Expression of p63 in a mouse model of Brcal mutation related breast cancer. Poster presented at the Annual Meeting of the American Association for Cancer Research, Washington, DC (Meeting Abstracts)... 

Hashizume, R., et al., The RING heterodimer BRCAl-BARDl is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J Biol Chem, 2001, 276(18), 14537-40. 

Strohmaier, H. et al. Human F-box protein hCdc4 targets cydin F for proteolysis and is mutated in a breast cancer cell line. Nature 2001, 413,... 

The molecular interactions between PTEN and FAK were studied in glioblastoma and breast cancer cells lacking PTEN. The PTEN trapping mutant bound wild-type FAK, requiring FAK autophosphorylation site Tyr397. In PTEN-mutated cancer cells, FAK phosphorylation was retained even in suspension after detachment from extracellular matrix, accompanied by enhanced PI3-K association with FAK and sustained PI3-K activity. PTEN-mutated cells were resistant to apoptosis in suspension, but most of the cells entered apoptosis after expression of exogenous PTEN or... 

A second group of inherited colon cancers are termed hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC may account for 5% of all colon cancer cases and can be caused by mutations in any of five different genes. All of these genes encode proteins involved in DNA mismatch repair (Fig II-5-3). As with inherited breast cancer, fiiulty DNA repair leads to mutated cells capable of producing tumors. 

For many common diseases, subsets of cases exist in which genetic factors play an especially important role. These subsets tend to develop disease early in life (e.g., BRCAl and BRCA2 mutations in breast cancer), and they often tend to have a more severe expression of the disease (e.g., APC mutations in colon cancer). 

Individuals at risk for developing a genetic disease with a delayed age of onset may wish to learn whether they have inherited a disease-causing mutation (e.g., Huntington disease, femilial breast cancer, hemochromatosis, adenomatous polyposis coli). In some cases, presymptomatic diagnosis can be highly usefiil in preventing serious disease consequences before they occur (e.g., phlebotomy for hemochromatosis, early tumor detection for familial breast cancer). 

Mutation detection — Genetic mutations leading to disease states such as familial breast cancer can be detected by arrays, provided that sufficient gene probe sequence content is available in order to make a statistically significant prognosis. 

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