Germline Genetic Testing
Hereditary Panels
Germline genetic testing analyses DNA from normal cells (typically from saliva or blood) to identify inherited mutations that significantly increase cancer risk. Unlike tumour sequencing, which examines mutations within the cancer itself, germline testing looks at your constitutional DNA — the code present in every cell of your body from birth. A positive finding means that close biological relatives have a 50% chance of carrying the same mutation and may benefit from preventive screening or risk-reduction strategies.
What It Measures
- BRCA1 and BRCA2 — hereditary breast and ovarian cancer syndrome
- Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM) — colorectal, endometrial, and other cancers
- PALB2, CHEK2, ATM — moderate-risk breast cancer genes
- APC — familial adenomatous polyposis (colon cancer)
- TP53 — Li-Fraumeni syndrome (multiple cancer types)
- VHL, RET, SDHB/C/D — kidney, thyroid, adrenal cancers
- CDKN2A — familial melanoma and pancreatic cancer
- PTEN — Cowden syndrome (breast, thyroid, endometrial)
- Extended panels: 80–200+ genes covering all major hereditary cancer syndromes
How It Works
A saliva sample or blood draw is collected. DNA is extracted and analysed using next-generation sequencing across a predefined panel of cancer susceptibility genes. Laboratory scientists assess variants against population databases (gnomAD, ClinVar) and classify findings as: Pathogenic, Likely Pathogenic, Variant of Uncertain Significance (VUS), Likely Benign, or Benign. Genetic counselling is strongly recommended before and after testing to help interpret results and guide clinical decisions.
Who Should Consider This Test
- Those with a personal or family history of breast, ovarian, colorectal, or endometrial cancer
- Patients diagnosed with cancer under 50 years old
- Ashkenazi Jewish individuals (higher prevalence of BRCA founder mutations)
- Men with breast cancer (strong indicator of BRCA2 mutation)
- Patients with triple-negative breast cancer at any age
- Those with multiple primary cancers
- Relatives of known BRCA or Lynch syndrome carriers
Evidence Summary
Germline genetic testing for hereditary cancer syndromes has among the strongest evidence of any cancer-prevention tool. BRCA1/2 testing is guideline-standard (NCCN, ESMO, NICE) for breast and ovarian cancer. Prophylactic surgery in BRCA carriers reduces breast cancer risk by 90% and ovarian cancer risk by 80–96%. Lynch syndrome testing is now recommended universally for all colorectal cancer diagnoses. Population-based genetic screening studies (BRCA in the UK, Israel) demonstrate cost-effectiveness at scale. Over 50% of patients who test positive were not identified by conventional family history criteria — supporting broader panel testing.
Available Labs & Providers
This list is not exhaustive. Ask your oncologist or integrative physician for locally available options.
Important Considerations
- A negative result does not mean zero cancer risk — most cancers are not hereditary
- Variants of Uncertain Significance (VUS) require specialist counselling and periodic reclassification
- Psychological impact can be significant — genetic counselling before and after is essential
- A positive result has implications for the entire biological family — consider implications before testing
- Insurance discrimination laws vary by country — understand your local legal protections (e.g. GINA in USA, GS Act in UK)
- Direct-to-consumer tests (e.g. 23andMe) only test 3 BRCA variants — not a clinical-grade screen
Related Tests
Informational only. Not medical advice. Always consult your oncologist before ordering or acting on any diagnostic test.