One-page cheat sheet
Inherited cancer syndromes
The genes behind family cancers, and the surgery that prevents them
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Red flags
- Cancer at a young age (under 50)
- Bilateral cancer or two primaries
- Several relatives on one side
- Rare cancers: male breast, medullary thyroid, adrenocortical
Breast and ovary
- BRCA1/BRCA2: breast, ovary; BRCA2 also prostate, pancreas, male breast
- Risk-reducing mastectomy; salpingo-oophorectomy when the family is complete
- PARP inhibitors for BRCA-mutated cancers
Bowel
- Lynch (MLH1, MSH2, MSH6, PMS2): right colon, endometrium, ovary, stomach, urinary tract
- Amsterdam 3-2-1; test every colorectal cancer for mismatch repair
- FAP (APC): thousands of polyps; prophylactic colectomy in late teens or twenties
- MUTYH: recessive polyposis
- Peutz-Jeghers (STK11): hamartomas, lip pigmentation
Endocrine
- MEN 1: parathyroid, pancreas, pituitary
- MEN 2A (RET): medullary thyroid, phaeochromocytoma, parathyroid
- MEN 2B (RET): medullary thyroid, phaeochromocytoma, mucosal neuromas
- Prophylactic thyroidectomy timed by the RET mutation; exclude phaeo first
- VHL: kidney, phaeo, haemangioblastoma
Others
- Li-Fraumeni (TP53): sarcoma, early breast, brain, adrenocortical; avoid radiation
- CDH1: diffuse gastric and lobular breast; prophylactic total gastrectomy
- Cowden (PTEN): breast, follicular thyroid, endometrium
What to do
- Draw a three-generation family tree
- Refer to clinical genetics for counselling and testing
- Test the affected person first, then relatives for the known variant
- Most are autosomal dominant: 50% risk to each child
Exam pearls
- Two-hit hypothesis: inherited cancers need only one more hit
- Germline = family; somatic = tumour only
- MSI-high tumours respond well to immunotherapy