48. Other Genetic Conditions Linked to Increased Cancer Risk
Hereditary susceptibility to breast cancer occurs in several other rare genetic conditions. Breast cancer is the most common adult manifestation of Li-Fraumeni syndrome, a multiple cancer syndrome caused by germline mutations in the TP53 gene. Breast cancer also is the most frequent malignancy diagnosed in Cowden syndrome, a condition with germline mutations in the PTEN gene. Both benign and malignant breast tumors occur in Muir-Torre syndrome, a condition related to hereditary nonpolyposis colon cancer (HNPCC), characterized by germline mutations in the DNA mismatch repair genes MSH2 and MLH1. Patients with Peutz-Jeghers syndrome display abnormal pigmentation, gastrointestinal polyps, and, if they are women, they are at increased risk for breast cancer and they experience early onset bilateral disease.