Li-Fraumeni Syndrome Cancer Associations
Li-Fraumeni syndrome is associated with breast cancer, not colon, ovarian, or lung cancer. The core cancers in Li-Fraumeni syndrome include soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, brain tumors, and adrenocortical carcinoma. 1
Core Cancers Associated with Li-Fraumeni Syndrome
Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome caused by germline mutations in the TP53 tumor suppressor gene. The syndrome is characterized by a specific pattern of malignancies:
- Soft tissue sarcomas - One of the most common cancers in LFS 1
- Osteosarcomas - Bone tumors that typically present at younger ages 1
- Premenopausal breast cancer - Particularly early-onset breast cancer 1
- Brain tumors - Including gliomas, choroid plexus carcinomas, and SHH subtype medulloblastomas 1
- Adrenocortical carcinoma - Rare cancer of the adrenal cortex 1
- Leukemia - Hematologic malignancies, including hypodiploid acute lymphoblastic leukemia 1
Cancer Risk and Penetrance
The cancer risk in individuals with Li-Fraumeni syndrome is extremely high:
- Nearly 100% lifetime cumulative cancer incidence 1
- By age 70, women have a 54% risk of breast cancer, 15% risk of soft tissue sarcoma, 6% risk of brain cancer, and 5% risk of osteosarcoma 1
- Men have a 22% risk of soft tissue sarcoma, 19% risk of brain cancer, and 11% risk of osteosarcoma by age 70 1
- Multiple primary cancers are common in affected individuals 1, 2
Additional Associated Cancers
Beyond the core cancers, LFS is also associated with:
- Gastric cancer 1, 3
- Colon cancer 1
- Bronchoalveolar cancer 1
- Thyroid cancer 3
- Melanoma (suggested by case reports) 1
Clinical Implications
Understanding the cancer spectrum in LFS is critical for several reasons:
- Early diagnosis allows for appropriate surveillance protocols 1
- Radiation exposure should be minimized due to increased risk of radiation-induced secondary malignancies 2
- Breast cancer management differs from standard protocols, often favoring total mastectomy over lumpectomy with radiation 3
- Screening should include whole-body MRI and other targeted imaging to detect cancers early 4, 3
Genetic Basis
- LFS is caused by germline mutations in the TP53 gene, located on chromosome 17 5
- The p53 protein functions as the "guardian of the genome" by controlling cell cycle and apoptosis 5
- Germline mutations in TP53 are found in over 50% of families meeting classic LFS criteria 1
- The type of TP53 mutation may influence disease penetrance and cancer spectrum 5
In summary, breast cancer is one of the core cancers associated with Li-Fraumeni syndrome, making option D the correct answer. Colon cancer can occur in LFS but is not considered a core cancer. Ovarian and lung cancers are not among the primary cancers associated with this syndrome.