Hereditary cancer syndromes: the table to know !
- Topic
A few families inherit a faulty cancer gene. Their cancers appear younger, in several organs and in several relatives.
Updated 2026-11-01
What it is
Hereditary cancer syndromes are caused by germline variants in tumour suppressor genes, DNA repair genes or, less often, oncogenes. Most are inherited as autosomal dominant traits, yet behave recessively in the cell: one mutated copy is inherited and the second is lost in the tissue (the two-hit hypothesis). Recognizing them changes care for the whole family: genetic counselling, early screening and risk-reducing surgery.
Key facts
- Two-hit hypothesis: the first hit is inherited in every cell; the second occurs in one tissue cell, so tumours come early and are often bilateral or multiple.
- DNA repair syndromes with autosomal recessive inheritance: xeroderma pigmentosum, Bloom syndrome, Fanconi anaemia, ataxia-telangiectasia.
- MEN 2 is the classic syndrome caused by a gain-of-function oncogene (RET).
- Lynch tumours show microsatellite instability and loss of mismatch repair proteins on immunohistochemistry.
Hereditary cancer syndromes to know
| Syndrome | Gene | Inheritance | Main tumours |
|---|---|---|---|
| Lynch syndrome | Mismatch repair: MLH1, MSH2, MSH6, PMS2 (EPCAM) | AD | Colorectal (right side, microsatellite instability), endometrial, ovarian, gastric, urinary tract |
| Familial adenomatous polyposis | APC | AD | Hundreds to thousands of colonic adenomas; colorectal cancer almost certain without colectomy |
| Hereditary breast and ovarian cancer | BRCA1, BRCA2 | AD | Breast, ovary, prostate, pancreas; male breast cancer with BRCA2 |
| Li–Fraumeni syndrome | TP53 | AD | Sarcomas, breast cancer at a young age, brain tumours, adrenocortical carcinoma, leukaemia |
| Hereditary retinoblastoma | RB1 | AD | Bilateral retinoblastoma, later osteosarcoma |
| MEN 1 | MEN1 (menin) | AD | Parathyroid, pituitary and pancreatic neuroendocrine tumours |
| MEN 2A and 2B | RET (oncogene) | AD | Medullary thyroid carcinoma, phaeochromocytoma; 2A parathyroid; 2B mucosal neuromas |
| Neurofibromatosis type 1 and 2 | NF1; NF2 | AD | NF1 neurofibromas and optic glioma; NF2 bilateral vestibular schwannomas and meningiomas |
| Von Hippel–Lindau | VHL | AD | Haemangioblastomas, clear cell renal carcinoma, phaeochromocytoma |
| Xeroderma pigmentosum | Nucleotide excision repair genes | AR | Skin cancers in childhood |
Clinical notes
- Red flags: cancer at a young age, several primary cancers in one person, bilateral tumours, several relatives on one side, rare tumours (male breast cancer).
- Carriers are offered earlier and more frequent screening (colonoscopy, breast MRI) and sometimes risk-reducing surgery (colectomy, salpingo-oophorectomy, thyroidectomy in RET carriers).
- Testing one patient informs relatives: cascade testing after genetic counselling.
- BRCA-mutated tumours respond to PARP inhibitors because they already lack homologous recombination repair.
Test yourself
Think of the answer, then tap the question to see it.
Why do hereditary cancer syndromes cause tumours at a younger age?
Every cell already carries the first hit, so only one more somatic mutation is needed to lose the gene's function.
Which genes are mutated in Lynch syndrome and what is the tumour's molecular hallmark?
Mismatch repair genes (MLH1, MSH2, MSH6, PMS2); the tumours show microsatellite instability.
Which syndrome is caused by germline TP53 mutations?
Li–Fraumeni syndrome: sarcomas, early breast cancer, brain tumours, adrenocortical carcinoma and leukaemia.
Which gene is mutated in MEN 2, and which tumour is present in almost all carriers?
The RET proto-oncogene; medullary thyroid carcinoma.
Which two hereditary cancer syndromes are autosomal recessive?
Xeroderma pigmentosum and Fanconi anaemia (also Bloom syndrome and ataxia-telangiectasia), all DNA repair defects.
Related
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
- Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum
- Multistep carcinogenesis: the adenoma–carcinoma sequence
- Mendelian inheritance: autosomal dominant, recessive and X-linked
- Cancer epidemiology: age, environment, predisposing conditions (and Colombia)
- Molecular pathology: PCR, FISH, sequencing and liquid biopsy
- Tumours of infancy and childhood
Related conditions
- Lynch syndrome (hereditary non-polyposis colorectal cancer)
- Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)
- Retinoblastoma
- Colorectal polyps and hereditary polyposis syndromes (FAP, Lynch)
- Multiple endocrine neoplasia (MEN 1, 2A, 2B)
- Neurofibromatosis (types 1 and 2)
- Xeroderma pigmentosum
- Medullary thyroid carcinoma
- Phaeochromocytoma
- Hereditary paraganglioma and pheochromocytoma (SDH)
- Bloom syndrome
- Fanconi anaemia
- Ataxia-telangiectasia
- Tuberous sclerosis complex
- Colorectal cancer
- Breast cancer
- Ovarian cancer
Elsewhere in DurgiPedia
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: The Genetics of Cancer (National Cancer Institute (NCI), 2026); Lynch syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Multiple endocrine neoplasia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); BRCA1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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