Which of the following chromosomal and/or genetic abnormalities is/are associated with the development of breast cancer?

a. Mutations in the p53 tumor suppressor gene

b. A mutation in the short arm of chromosome 2

c. The presence of a BRCA 1 gene on chromosome 17

d. The presence of the BRCA 2 gene on chromosome 13

There are four inherited syndromes associated with the development of breast cancer. The Li-Fraumeni syndrome has an autosomal dominant mode of inheritance. The syndrome is attributed to mutations in the p53 tumor suppressor gene, a gene that codes for a protein that serves as a G1-S checkpoint regulator of the cell cycle. More recently, a mutation has been characterized on the short arm of chromosome 2 in a gene associated with DNA repair. Predisposition to a wide range of malignancies, including breast and colon cancer is associated with abnormalities at this locus. The most exciting development in inherited susceptibility to breast cancer relate to the identification and cloning of the BRCA 1 gene, which was initially localized on the long arm of chromosome 17 by linkage analysis. Germline abnormalities in BRCA a may be responsible for as many as 5% of all breast cancers in the United States. The gene is characterized by autosomal dominant inheritance with a high degree of penetrance. Almost 60% of women inheriting the gene will develop breast cancer by age 50, and a lifelong risk approaches 85%. Another breast cancer susceptibility gene, dubbed BRCA 2, has been localized by linkage analysis to a small region of chromosome 13q12-13. BRCA 2 apparently confers the high-risk of early onset female breast cancer. Similar to BRCA 1, the lifetime breast cancer risk approaches 90% in carriers of this gene.