Perhaps 8-10% of breast cancer is familial. BRCA-1 mutations account for about 5%. BRCA-1 maps to chromosome 17q21 and appears to be involved in transcription-coupled DNA repair. Ashkenazi Jewish women have a 1% chance of having a common mutation (deletion of adenine and guanine at position 185). The BRCA-1 syndrome includes an increased risk of ovarian cancer in women and prostate cancer in men. BRCA-2 on chromosome 11 may account for 2-3% of breast cancer. Mutations are associated with an increased risk of breast cancer in men and women. Germ-line mutations in p53 (Li-Fraumeni syndrome) are very rare, but breast cancer, sarcomas, and other malignancies occur in such families. Germ-line mutations in PALB2, hCHK2, and PTEN may account for some familial breast cancer. Sporadic breast cancers show many genetic alterations, including overexpression of HER2/neu in 25% of cases, p53 mutations in 40%, and loss of heterozygosity at other loci.