{"entity":{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","aka":[],"tldr":"A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.","summary":"Germline testing sequences DNA from blood or saliva by next-generation sequencing to find inherited pathogenic variants, as distinct from tumour-only sequencing that picks up acquired mutations. Multi-gene hereditary panels (BRCA1/2, PALB2, TP53, Lynch genes, CDH1, ATM, CHEK2) are recommended for all TNBC, ovarian, pancreatic, and metastatic prostate cancer patients and increasingly for all breast cancer. Findings change surgery, drug choice (PARP inhibitors), and family screening, because relatives can be cascade-tested and offered surveillance or risk-reducing measures. The test itself is cheap and actionable, but variants of uncertain significance remain a burden and counselling capacity limits uptake. The simple version is that this test reads the DNA a person was born with, and a positive result can protect a whole family, not just one patient.","status":"standard-of-care","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Genetic_testing","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Genetic_testing"},{"label":"Pancreatic Cancer UK: family history of pancreatic cancer","url":"https://www.pancreaticcancer.org.uk/information-and-support/family-history-of-pancreatic-cancer/"},{"label":"Pancreatic Cancer UK: hereditary pancreatic cancers","url":"https://www.pancreaticcancer.org.uk/information-and-support/family-history-of-pancreatic-cancer/hereditary-pancreatic-cancers/"},{"label":"Macmillan: BRCA1 and BRCA2 genes","url":"https://www.macmillan.org.uk/cancer-information-and-support/worried-about-cancer/causes-and-risk-factors/brca-gene"},{"label":"NICE NG85: pancreatic cancer in adults, diagnosis and management, recommendations","url":"https://www.nice.org.uk/guidance/ng85/chapter/Recommendations"},{"label":"NICE TA750: olaparib maintenance for BRCA mutation-positive metastatic pancreatic cancer (terminated appraisal, December 2021)","url":"https://www.nice.org.uk/guidance/terminated/ta750"},{"label":"Golan et al., maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, POLO (NEJM 2019)","url":"https://doi.org/10.1056/NEJMoa1903387"},{"label":"Bowel Cancer UK: Lynch syndrome","url":"https://www.bowelcanceruk.org.uk/campaigning/never-too-young/lynch-syndrome/"},{"label":"Bowel Cancer UK: family history","url":"https://www.bowelcanceruk.org.uk/about-bowel-cancer/risk-factors/family-history/"},{"label":"NHS: genetic and genomic testing","url":"https://www.nhs.uk/tests-and-treatments/genetic-and-genomic-testing/"},{"label":"NICE NG151: colorectal cancer, recommendations","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"NICE NG122: lung cancer, diagnosis and staging","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":[],"related":["germline-to-parp"],"cancers":["tnbc","ovarian","prostate","pancreatic","colorectal","lung-cancer","nsclc"],"sections":["diagnostics","prevention"],"technologies":[],"targets":["brca","tp53"],"drugs":[],"companies":["outcomes4me","yemaachi-biotech"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","paper-shindo-germline-sporadic-pancreatic-jco-2017","paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018","paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019","paper-moreira-lynch-syndrome-identification-jama-2012","paper-ligtenberg-epcam-deletion-msh2-silencing-nat-genet-2009","paper-palles-germline-pole-pold1-proofreading-nat-genet-2013"],"journals":["familial-cancer"],"dependsOn":[],"notes":["Pancreatic cancer: about one in ten cases runs in families (Pancreatic Cancer UK). A germline BRCA1 or BRCA2 result changes treatment (platinum chemotherapy is favoured; in POLO maintenance olaparib lengthened the time before growth) and matters for relatives, who may be offered testing and, under NICE NG85, MRI/MRCP or EUS surveillance if they carry BRCA1, BRCA2, PALB2 or CDKN2A and have a first-degree relative with the cancer. NICE's appraisal of olaparib in pancreatic cancer (TA750) was terminated without a recommendation, so NHS funding is a question for your team.","Pancreatic cancer: a pathogenic germline variant is found in 4 to 10% of unselected patients on focused panels and 19.8% on a 76-gene panel, and only 3 of 33 carriers in one series had a family history of pancreatic cancer, so testing is offered at diagnosis regardless of history (Shindo 2017, Hu 2018, Lowery 2018). The result selects platinum and olaparib maintenance and opens surveillance for relatives.","Bowel cancer: Bowel Cancer UK says Lynch syndrome is estimated to cause around 3 percent of bowel cancer cases in the UK each year, that testing should be offered at diagnosis because the condition can affect treatment options, and that if a person has it there is a 50 percent chance their children, brothers and sisters do too, so relatives should be offered the same test (cascade testing). NICE NG151 says to consider aspirin daily for more than 2 years to reduce the risk of colorectal cancer in people with Lynch syndrome, an off-label use in January 2020 with a NICE patient decision aid to support the discussion.","Colorectal cancer: the germline questions are Lynch syndrome (MLH1, MSH2, MSH6, PMS2 and 3' EPCAM deletions, which need copy-number analysis rather than sequencing; Ligtenberg 2009) and the polymerase proofreading syndromes (POLE p.Leu424Val and POLD1 p.Ser478Asn in patients with many adenomas or early-onset disease; Palles 2013). Universal tumour mismatch repair testing is the trigger for the first (Moreira 2012).","Lung cancer: most genomic testing in lung cancer is done on the tumour and says nothing about what you may have passed on, which is worth saying plainly because the two kinds of test are easily confused. The NHS explains the difference between genetic testing for inherited conditions and genomic testing of a tumour to guide treatment; NICE NG122 (1.2.12) points teams to the National Genomics Test Directory for the tumour panels."],"principle":"NGS of blood or saliva DNA identifies pathogenic germline variants.","strengths":["Actionable for patient and relatives","Cheap"],"limitations":["VUS burden","Uptake and counselling capacity"]},"route":"/technologies/germline-testing/","neighbours":{"pairing":[{"id":"germline-to-parp","kind":"pairing","name":"Germline BRCA test → adjuvant PARP inhibitor","route":"/pairings/germline-to-parp/"}],"cancer":[{"id":"aya-cancers","kind":"cancer","name":"Adolescent and young adult cancers (ages 15 to 39)","route":"/cancers/aya-cancers/"},{"id":"adrenocortical","kind":"cancer","name":"Adrenocortical carcinoma","route":"/cancers/adrenocortical/"},{"id":"atrt","kind":"cancer","name":"Atypical teratoid/rhabdoid tumour 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the prostate","route":"/cancers/prostate-ductal-adenocarcinoma/"},{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"early-onset-colorectal","kind":"cancer","name":"Early-onset colorectal cancer (under 50)","route":"/cancers/early-onset-colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"fap-associated-colorectal-cancer","kind":"cancer","name":"Familial adenomatous polyposis-associated colorectal cancer","route":"/cancers/fap-associated-colorectal-cancer/"},{"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":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hereditary-ppgl","kind":"cancer","name":"Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)","route":"/cancers/hereditary-ppgl/"},{"id":"hr-positive-early-high-risk","kind":"cancer","name":"High-risk early HR-positive breast cancer","route":"/cancers/hr-positive-early-high-risk/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hyperparathyroidism-jaw-tumour-syndrome","kind":"cancer","name":"Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma)","route":"/cancers/hyperparathyroidism-jaw-tumour-syndrome/"},{"id":"localised-adrenocortical-carcinoma","kind":"cancer","name":"Localised adrenocortical carcinoma (ENSAT stage I to III, resectable)","route":"/cancers/localised-adrenocortical-carcinoma/"},{"id":"localised-small-bowel-adenocarcinoma","kind":"cancer","name":"Localised small bowel adenocarcinoma (stage I to III, resected)","route":"/cancers/localised-small-bowel-adenocarcinoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"lynch-associated-colorectal-cancer","kind":"cancer","name":"Lynch syndrome-associated colorectal cancer","route":"/cancers/lynch-associated-colorectal-cancer/"},{"id":"male-breast-cancer","kind":"cancer","name":"Male breast cancer","route":"/cancers/male-breast-cancer/"},{"id":"metastatic-ppgl","kind":"cancer","name":"Metastatic pheochromocytoma and paraganglioma","route":"/cancers/metastatic-ppgl/"},{"id":"gastric-msi-high","kind":"cancer","name":"Microsatellite-unstable (MSI-high) gastric cancer","route":"/cancers/gastric-msi-high/"},{"id":"msi-high-pdac","kind":"cancer","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","route":"/cancers/msi-high-pdac/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"},{"id":"endometrial-mmr-deficient","kind":"cancer","name":"Mismatch-repair-deficient endometrial cancer","route":"/cancers/endometrial-mmr-deficient/"},{"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":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"paediatric-high-grade-glioma","kind":"cancer","name":"Paediatric high-grade glioma (excluding diffuse midline glioma)","route":"/cancers/paediatric-high-grade-glioma/"},{"id":"paediatric-low-grade-glioma","kind":"cancer","name":"Paediatric low-grade glioma","route":"/cancers/paediatric-low-grade-glioma/"},{"id":"pancreatic-acinar-cell-carcinoma","kind":"cancer","name":"Pancreatic acinar cell carcinoma","route":"/cancers/pancreatic-acinar-cell-carcinoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"pancreatic-net","kind":"cancer","name":"Pancreatic neuroendocrine tumours","route":"/cancers/pancreatic-net/"},{"id":"pancreatoblastoma","kind":"cancer","name":"Pancreatoblastoma","route":"/cancers/pancreatoblastoma/"},{"id":"parathyroid-carcinoma","kind":"cancer","name":"Parathyroid carcinoma","route":"/cancers/parathyroid-carcinoma/"},{"id":"pheochromocytoma-paraganglioma","kind":"cancer","name":"Pheochromocytoma and paraganglioma 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