{"entity":{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","aka":["hereditary cancer","hereditary cancers","hereditary cancer syndrome","inherited cancer","inherited cancer syndrome","inherited risk","cancer predisposition","cancer susceptibility","familial cancer"],"tldr":"About 5-10% of cancers arise from an inherited gene fault. Recognising the syndromes (BRCA, Lynch, Li-Fraumeni, VHL, MEN, FAP, retinoblastoma and dozens more) changes screening, surgery and treatment for the patient and their relatives.","summary":"The main syndromes: hereditary breast-ovarian (BRCA1/2, PALB2), Lynch (MLH1/MSH2/MSH6/PMS2/EPCAM; colorectal, endometrial, urothelial and more), Li-Fraumeni (TP53; sarcoma, breast, brain, adrenocortical, leukaemia; whole-body MRI surveillance halves cancer mortality), familial adenomatous polyposis (APC), von Hippel-Lindau (VHL; RCC, phaeochromocytoma, haemangioblastoma; belzutifan approved 2021), MEN1/MEN2 (RET; medullary thyroid), hereditary retinoblastoma (RB1), Peutz-Jeghers, Cowden (PTEN), hereditary diffuse gastric cancer (CDH1), hereditary paraganglioma (SDHx), DICER1, and moderate-penetrance genes (CHEK2, ATM). Practice: germline multigene panel testing is now recommended for all patients with ovarian, pancreatic, metastatic prostate, male breast, and many breast and colorectal cancers (NCCN), with cascade testing of relatives; risk-reducing surgery (mastectomy, salpingo-oophorectomy, colectomy, thyroidectomy), intensified surveillance (MRI, colonoscopy), chemoprevention (aspirin in Lynch, CAPP2), and therapy selection (PARP inhibitors, immunotherapy for Lynch tumours, belzutifan in VHL). Population-based BRCA/Lynch screening and polygenic risk scores are the frontier.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Hereditary_cancer_syndrome","links":[{"label":"NCCN Genetic/Familial High-Risk Assessment","url":"https://www.nccn.org/guidelines/guidelines-detail?category=2&id=1503"},{"label":"NCI Cancer Genetics Overview (PDQ)","url":"https://www.cancer.gov/about-cancer/causes-prevention/genetics/overview-pdq"}],"tags":["gap-fill","hereditary"],"related":["brca","lynch-syndrome","li-fraumeni","vhl-disease","germline-testing","risk-reducing-salpingectomy","retinoblastoma","adrenocortical","men1-hereditary-net","whole-body-mri","colectomy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["familial-cancer"],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},"route":"/terms/hereditary-cancer-syndromes/","neighbours":{"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"pold1","kind":"target","name":"POLD1","route":"/targets/pold1/"}],"term":[{"id":"bap1-loss","kind":"term","name":"BAP1 loss","route":"/terms/bap1-loss/"},{"id":"caps-consortium-pancreatic-screening","kind":"term","name":"CAPS: the Cancer of the Pancreas Screening consortium and its surveillance studies (CAPS1 to CAPS5)","route":"/terms/caps-consortium-pancreatic-screening/"},{"id":"cdkn2a-homozygous-deletion","kind":"term","name":"CDKN2A/B homozygous deletion","route":"/terms/cdkn2a-homozygous-deletion/"},{"id":"colectomy","kind":"term","name":"Colectomy","route":"/terms/colectomy/"},{"id":"early-detection-term","kind":"term","name":"Early detection","route":"/terms/early-detection-term/"},{"id":"founder-variant","kind":"term","name":"Founder variant","route":"/terms/founder-variant/"},{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"inherited-skin-cancer-syndromes","kind":"term","name":"Inherited syndromes that cause skin cancer: Gorlin syndrome and xeroderma pigmentosum","route":"/terms/inherited-skin-cancer-syndromes/"},{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","route":"/terms/li-fraumeni/"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","route":"/terms/lynch-syndrome/"},{"id":"men1-hereditary-net","kind":"term","name":"MEN1 and hereditary neuroendocrine syndromes","route":"/terms/men1-hereditary-net/"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","route":"/terms/mlh1-promoter-methylation/"},{"id":"pretext-chic","kind":"term","name":"PRETEXT and CHIC risk groups (hepatoblastoma)","route":"/terms/pretext-chic/"},{"id":"pten-loss","kind":"term","name":"PTEN loss","route":"/terms/pten-loss/"},{"id":"risk-factor","kind":"term","name":"Risk factor","route":"/terms/risk-factor/"},{"id":"sdh-deficiency","kind":"term","name":"SDH deficiency (SDHB immunohistochemistry loss)","route":"/terms/sdh-deficiency/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"},{"id":"tumour-suppressor-gene","kind":"term","name":"Tumour suppressor gene","route":"/terms/tumour-suppressor-gene/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"},{"id":"vhl-disease","kind":"term","name":"Von Hippel-Lindau disease","route":"/terms/vhl-disease/"},{"id":"wilms-risk-markers","kind":"term","name":"Wilms tumour risk markers (anaplasia, 1p/16q loss, 1q gain, SIOP and COG risk groups)","route":"/terms/wilms-risk-markers/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"risk-reducing-salpingectomy","kind":"technology","name":"Risk-reducing and opportunistic salpingectomy","route":"/technologies/risk-reducing-salpingectomy/"},{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","route":"/technologies/whole-body-mri/"}],"cancer":[{"id":"adrenocortical","kind":"cancer","name":"Adrenocortical carcinoma","route":"/cancers/adrenocortical/"},{"id":"ampullary","kind":"cancer","name":"Ampullary cancer (ampulla of Vater)","route":"/cancers/ampullary/"},{"id":"atrt","kind":"cancer","name":"Atypical teratoid/rhabdoid tumour (ATRT)","route":"/cancers/atrt/"},{"id":"pleuropulmonary-blastoma","kind":"cancer","name":"Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)","route":"/cancers/pleuropulmonary-blastoma/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"fh-deficient-renal-cell-carcinoma","kind":"cancer","name":"Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated)","route":"/cancers/fh-deficient-renal-cell-carcinoma/"},{"id":"hereditary-ppgl","kind":"cancer","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/cancers/hereditary-ppgl/"},{"id":"hyperparathyroidism-jaw-tumour-syndrome","kind":"cancer","name":"Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma)","route":"/cancers/hyperparathyroidism-jaw-tumour-syndrome/"},{"id":"localised-small-bowel-adenocarcinoma","kind":"cancer","name":"Localised small bowel adenocarcinoma (stage I to III, resected)","route":"/cancers/localised-small-bowel-adenocarcinoma/"},{"id":"male-breast-cancer","kind":"cancer","name":"Male breast cancer","route":"/cancers/male-breast-cancer/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men1-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 1 (MEN1)","route":"/cancers/men1-syndrome/"},{"id":"men2-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)","route":"/cancers/men2-syndrome/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"parathyroid-carcinoma","kind":"cancer","name":"Parathyroid carcinoma","route":"/cancers/parathyroid-carcinoma/"},{"id":"pheochromocytoma-paraganglioma","kind":"cancer","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/cancers/pheochromocytoma-paraganglioma/"},{"id":"rare-childhood-cancers","kind":"cancer","name":"Rare cancers of childhood (NCI PDQ umbrella)","route":"/cancers/rare-childhood-cancers/"},{"id":"retinoblastoma","kind":"cancer","name":"Retinoblastoma","route":"/cancers/retinoblastoma/"},{"id":"small-bowel","kind":"cancer","name":"Small intestine cancer (small bowel adenocarcinoma)","route":"/cancers/small-bowel/"},{"id":"sdh-deficient-renal-cell-carcinoma","kind":"cancer","name":"Succinate dehydrogenase-deficient renal cell carcinoma","route":"/cancers/sdh-deficient-renal-cell-carcinoma/"}],"journal":[{"id":"familial-cancer","kind":"journal","name":"Familial cancer","route":"/journals/familial-cancer/"}],"paper":[{"id":"paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","kind":"paper","name":"Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer","route":"/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/"},{"id":"paper-palles-germline-pole-pold1-proofreading-nat-genet-2013","kind":"paper","name":"Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas","route":"/key-papers/paper-palles-germline-pole-pold1-proofreading-nat-genet-2013/"},{"id":"paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","kind":"paper","name":"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1","route":"/key-papers/paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009/"},{"id":"paper-moreira-lynch-syndrome-identification-jama-2012","kind":"paper","name":"Identification of Lynch syndrome among patients with colorectal cancer","route":"/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/"},{"id":"paper-caps-consortium-surveillance-recommendations-gut-2020","kind":"paper","name":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","route":"/key-papers/paper-caps-consortium-surveillance-recommendations-gut-2020/"},{"id":"paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016","kind":"paper","name":"Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer","route":"/key-papers/paper-roberts-familial-pancreatic-whole-genome-cancer-discov-2016/"}],"person":[{"id":"angelina-jolie","kind":"person","name":"Angelina Jolie","route":"/people/angelina-jolie/"},{"id":"gilda-radner","kind":"person","name":"Gilda Radner","route":"/people/gilda-radner/"},{"id":"jon-huntsman","kind":"person","name":"Jon M. Huntsman Sr.","route":"/people/jon-huntsman/"},{"id":"mary-claire-king","kind":"person","name":"Mary-Claire King","route":"/people/mary-claire-king/"}],"institution":[{"id":"ac-camargo","kind":"institution","name":"A.C. Camargo Cancer Center","route":"/institutions/ac-camargo/"},{"id":"hcpa-porto-alegre","kind":"institution","name":"Hospital de Clínicas de Porto Alegre","route":"/institutions/hcpa-porto-alegre/"}],"pathway":[{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"oncogene-activation-two-hit","kind":"pathway","name":"Drivers, passengers & the two-hit model","route":"/pathways/oncogene-activation-two-hit/"}],"collection":[{"id":"force-facing-our-risk","kind":"collection","name":"FORCE: Facing Our Risk of Cancer Empowered","route":"/collections/force-facing-our-risk/"},{"id":"nhs-jewish-brca-testing","kind":"collection","name":"NHS Jewish BRCA Testing Programme","route":"/collections/nhs-jewish-brca-testing/"},{"id":"sharsheret","kind":"collection","name":"Sharsheret","route":"/collections/sharsheret/"}]}}