Breast cancer inherited

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

The two-hit model applies to a number of other inherited neoplasias, including familial breast cancer, familial colon cancer, familial melanoma, and neurofibromatosis. 

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. 

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). 

For example, female first-degree relatives of women who have had breast cancer have a risk of breast cancer 2-3 times as great as normal, but the data do not fit any simple hypothesis. For most cancers, heritability is rather low. Therefore, the mutation component is likely to be low. There may be a mutation component acting through both germinal and somatic effects. If the two-mutation hypothesis for childhood tumors is correct, an environmental chemical could increase not only the frequency with which the first mutation would be inherited but also the frequency with which the second, somatic mutation would occur. Most calculations concerning retinoblastoma assume that the second mutation is almost certain to happen somewhere in the retina, provided that the first, inherited mutant gene is present. 

Robson ME, Offit K. Considerations in genetic counseling for inherited breast cancer predisposition. Sem Rad Oncol 2002 12 362-70. 

Women who inherit one TtmlmiBRCAl gene have a 60 percent chance of developing breast cancer by the age of 50. The protein produced by the BRCAl gene has been found to be involved in the repair of DNA double-strand breaks. Which of the following processes is most likely to be adversely affected by a deficiency in the BRCAl protein ... 

Inactivation of BRCAl, a gene that appears to operate in DNA repair pathways that appear generic to various cell types, predisposes women to inherited forms of breast cancer, but the exact mechanism has been elusive. 

Couch FI, Weber BL. Breast cancer. In Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic and Molecular Basis of Inherited Disease, 8th ed. New York McGraw-Hill, 2001 999-1031. 

Mutations occur at a DNA level and can give rise to a different protein product. This can be the cause of an inherited disease, such as breast cancer or cystic fibrosis) or indicate a condition. 

Defects in repair by homologous recombination are associated with inheritance of one mutant allele of the BRCA-1 or BRCA-2 gene and result in predisposition to breast cancer. 

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