What is precision medicine?

Precision medicine (also called personalised medicine) is an approach to medical treatment that considers individual biological variation — particularly genetic variation — to guide decisions about prevention, diagnosis and treatment. The goal: the right treatment for the right patient at the right dose at the right time. This contrasts with the traditional "one-size-fits-all" approach where the same drug at the same dose is prescribed to everyone with a given diagnosis, even though individual variation in drug metabolism, target receptor genetics and tumour biology means responses differ dramatically. Precision medicine has been most developed in: oncology (tumour biomarker-directed targeted therapy); pharmacogenomics (genetic variants affecting drug metabolism and response); hereditary disease risk (BRCA, Lynch syndrome).

What is pharmacogenomics?

Pharmacogenomics studies how genetic variation affects an individual's response to drugs — including: drug metabolism (how quickly the liver breaks down a drug — too slow → toxicity; too fast → no effect); drug targets (variation in receptor genes affects drug binding and response); drug transporters (variation in P-glycoprotein and organic anion transporters affects drug distribution). Clinical examples: CYP2D6 and codeine (poor metabolisers get no analgesia; ultra-rapid metabolisers risk toxicity); CYP2C19 and clopidogrel (poor metabolisers have reduced antiplatelet effect after PCI); HLA-B*5701 and abacavir (carriers develop life-threatening hypersensitivity — screened before prescription); HLA-B*5801 and allopurinol (carriers in East Asian populations risk severe cutaneous reactions).

Should everyone get genetic testing?

Not at present — genetic testing should be targeted, not universal. Situations where genetic testing is clinically recommended: personal or family history of hereditary cancer (BRCA1/2 testing if breast/ovarian/prostate cancer at young age or in males; Lynch syndrome testing for colorectal or endometrial cancer); pharmacogenomics (before specific drugs where genetic variants affect safety — abacavir, clopidogrel in some centres, warfarin in some protocols, TPMT before thiopurines); rare/undiagnosed diseases (whole exome or genome sequencing through NHS GMS). Direct-to-consumer genetic testing (23andMe, Ancestry DNA): provides some health-relevant information (BRCA variants — limited panel; ApoE4 and Alzheimer's risk) but with important limitations: incomplete coverage of clinically relevant variants; no clinical genetic counselling; potential for significant anxiety and misinterpretation of results.

What is tumour biomarker testing in cancer?

Before starting cancer treatment, tumour biopsy or blood (liquid biopsy) is now commonly tested for specific biomarkers that guide therapy choice: HER2 amplification (breast, gastric cancer) → trastuzumab ± pertuzumab, T-DM1, lapatinib. EGFR mutation (NSCLC) → osimertinib (first-line, superior to chemotherapy). BRAF V600E (melanoma, NSCLC, CRC) → vemurafenib + cobimetinib; dabrafenib + trametinib. ALK/ROS1 rearrangement (NSCLC) → alectinib, lorlatinib, crizotinib. PD-L1 expression (multiple) → pembrolizumab, nivolumab, atezolizumab. MSI-H/dMMR (any solid tumour) → pembrolizumab (first pan-tumour approval by biomarker, FDA 2017). BRCA1/2 mutation (ovarian, breast, pancreatic, prostate) → PARP inhibitors. Without biomarker testing, patients may receive ineffective or unnecessary chemotherapy while missing targeted therapies with dramatically higher response rates.

Is whole genome sequencing available on the NHS?

Yes — through the NHS Genomics Medicine Service (GMS), launched in 2020 on the foundation of the 100,000 Genomes Project. Currently available via NHS GMS for: rare and undiagnosed diseases (referred through specialist rare disease clinical networks); cancer (tumour whole genome sequencing for selected haematological malignancies and solid tumours to guide treatment decisions). What is NOT currently available: population-wide whole genome sequencing for prevention; direct-to-consumer WGS through NHS (only through approved clinical pathways). The NHS GMS has committed to sequencing 5 million genomes by 2023-2028 — the most ambitious genomic medicine programme of any national health system.

How does GMJ News cover precision medicine?

GMJ News covers HLA-B*5701 abacavir screening (pharmacogenomics triumph), BRCA1/2 hereditary cancer risk, Lynch syndrome CRC prevention, companion diagnostics (HER2, EGFR, BRAF, MSI-H), pembrolizumab pan-tumour approval (first biomarker-only approval), CYP2D6 codeine toxicity, CYP2C19 and clopidogrel, PARP inhibitors (synthetic lethality), polygenic risk scores, NHS Genomics Medicine Service, and the 100,000 Genomes Project. Precision medicine is directly relevant to PHIG's cancer programme, Georgia's developing genetic services, and GMJ's role in translating genomic evidence to clinical practice.

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Precision & Genomic Medicine

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Precision medicine — treating the right patient with the right drug at the right dose at the right time using individual biological characteristics (genomic, proteomic, metabolomic) to guide clinical decisions — has moved from concept to daily clinical practice: HLA-B*5701 screening before abacavir prescription has virtually eliminated life-threatening hypersensitivity reactions in HIV treatment; CYP2D6 genotyping guides codeine, tamoxifen and antidepressant prescribing; BRCA1/2 testing (popularised by Angelina Jolie’s 2013 New York Times op-ed) guides cancer risk management and chemotherapy choice; and tumour biomarker profiling (HER2, EGFR, BRAF, PD-L1, MSI-H) now determines which cancer drug a patient receives rather than simply which organ their cancer arose from (WHO Genomics). The NHS Genomics Medicine Service (2020) and the 100,000 Genomes Project have established whole-genome sequencing as an NHS clinical service — positioning the UK at the global frontier of genomic medicine implementation.

Key messages

HLA-B*5701 screening — a pharmacogenomics triumph

Prospective HLA-B*5701 screening before abacavir (HIV drug) prescription has virtually eliminated severe hypersensitivity reactions — which affected approximately 5-8% of patients before screening and caused life-threatening multi-organ reactions. This is the clearest example of pharmacogenomics improving patient safety: a genetic test prevents a serious adverse drug reaction in 100% of susceptible patients identified.

BRCA1/2 — Angelina Jolie effect and cascade testing

BRCA1 mutations confer approximately 70-85% lifetime breast cancer risk and approximately 11-46% ovarian cancer risk. Angelina Jolie's 2013 New York Times op-ed disclosing her BRCA1 mutation and prophylactic bilateral mastectomy decision increased genetic testing rates by approximately 64% in the following months ("the Angelina Jolie effect"). Cascade testing (testing relatives of identified mutation carriers) can prevent multiple cancers per family.

Companion diagnostics — the right drug for the right tumour

Precision oncology now requires tumour biomarker testing before many treatments: HER2 amplification (breast, gastric cancer) → trastuzumab; EGFR mutation (NSCLC) → osimertinib; BRAF V600E (melanoma) → vemurafenib/dabrafenib; PD-L1 expression (multiple cancers) → pembrolizumab; MSI-H/dMMR (any solid tumour) → pembrolizumab (the first FDA approval across tumour types by biomarker alone). Biomarker-directed therapy dramatically improves response rates vs unselected treatment.

Pharmacogenomics beyond oncology — everyday prescribing

CYP2D6: codeine (poor metabolisers get no pain relief; ultra-rapid metabolisers risk toxicity — codeine is being phased out); tamoxifen (poor metabolisers have reduced active metabolite endoxifen — poorer cancer prevention outcomes); multiple antidepressants (amitriptyline, fluoxetine, paroxetine — altered metabolism). CYP2C19: clopidogrel (poor metabolisers have reduced antiplatelet effect — should receive prasugrel/ticagrelor after PCI). TPMT/NUDT15: azathioprine/mercaptopurine — poor metabolisers develop severe myelosuppression; screening now routine before initiation.

Polygenic risk scores — population-level genomic risk

Polygenic risk scores (PRS) integrate effects of thousands of common genetic variants (SNPs) to calculate individual disease risk. Clinical applications growing: coronary artery disease PRS identifies individuals with familial hypercholesterolaemia-level risk without a monogenic mutation (who would benefit from early statin therapy); breast cancer PRS refines population screening recommendations; type 2 diabetes PRS identifies prevention targets. Not yet as clinically actionable as monogenic variants — but rapidly improving.

NHS Genomics Medicine Service — whole genome sequencing in the NHS

The NHS Genomics Medicine Service (GMS), established 2020, provides whole genome sequencing (WGS) for: rare and undiagnosed diseases (30,000+ patients); cancer (tumour WGS to guide treatment). Building on the 100,000 Genomes Project (completed 2018 — 100,000 genomes from 85,000 NHS patients). The UK has the world's most established national genomic medicine infrastructure — with ambitions for 5 million genome sequencing by 2025-2028.

Key statistics

HLA-B*5701

screening before abacavir virtually eliminates severe hypersensitivity (PREDICT-1 trial)

NEJM 2008

~70-85%

lifetime breast cancer risk with BRCA1 mutation

NEJM/Cancer Research

64%

increase in BRCA testing after Angelina Jolie's 2013 op-ed (Jolie effect)

PLOS ONE 2014

MSI-H

first FDA cancer approval across tumour types by biomarker alone (pembrolizumab 2017)

FDA 2017

NHS GMS 2020

UK NHS Genomics Medicine Service — WGS for rare diseases and cancer

NHS England

100K genomes

100,000 Genomes Project completed 2018 — foundation of NHS genomic medicine

Genomics England

Precision medicine maturity — by application area (clinical readiness)

Source: FDA/NHS. Pharmacogenomics in oncology most mature; polygenic risk scoring emerging.

Glossary of key terms

Companion diagnostics (CDx)
FDAA diagnostic test (typically genetic biomarker assay) that is required or strongly recommended before a specific drug is prescribed — to identify patients most likely to benefit or avoid those likely to be harmed. FDA defines CDx as "a medical device, often an in vitro device, that provides information that is essential for the safe and effective use of a corresponding therapeutic product." Examples: PATHWAY Anti-HER2 (Roche) before trastuzumab; cobas EGFR Mutation Test v2 (Roche) before erlotinib in NSCLC; Foundation One CDx (Foundation Medicine) — comprehensive NGS panel identifying multiple biomarkers simultaneously for matched targeted therapy selection.

BRCA1/2 — pathogenic variants
NEJM/GeneticsBRCA1 and BRCA2 encode tumour suppressor proteins involved in homologous recombination DNA repair. Pathogenic variants: inherited in an autosomal dominant pattern; BRCA1 pathogenic variants in approximately 1 in 300-500 people; BRCA2 in approximately 1 in 400-800. BRCA1 mutation: breast cancer risk 72-85% lifetime; ovarian 38-46%; BRCA2: breast 69-80%; ovarian 11-18%. Testing indications: breast or ovarian cancer at young age; bilateral breast cancer; triple-negative breast cancer; family history of known BRCA mutation; Ashkenazi Jewish ancestry (founder mutations in approximately 2% of population). BRCA1/2 also associated with: pancreatic cancer (BRCA2 primarily), prostate cancer (BRCA2), melanoma.

Lynch syndrome (HNPCC)
Genetics/GastroenterologyThe most common hereditary colorectal cancer syndrome — caused by germline mutations in DNA mismatch repair genes: MLH1 (most common), MSH2, MSH6, PMS2. Lifetime colorectal cancer risk: approximately 40-80% (vs 5% general population). Also elevated risk: endometrial cancer (25-60%); ovarian (4-24%); gastric; urinary tract; brain. Diagnosis: microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) on tumour testing → germline testing. Universal CRC tumour screening for Lynch syndrome is now recommended (IHC/PCR on all CRC). Cascade testing of relatives is essential — colonoscopic surveillance from age 20-25 reduces CRC mortality.

CYP2D6 and codeine — a clinical safety issue
PharmacogenomicsCodeine is a prodrug — it requires CYP2D6 metabolism to convert to morphine (the active analgesic). CYP2D6 poor metabolisers (~7-10% of European population): cannot convert codeine → codeine is ineffective for analgesia AND can accumulate causing nausea. Ultra-rapid metabolisers (~1-3% Europeans; up to 10-30% in North African and Middle Eastern populations): convert codeine to morphine too rapidly → potentially fatal morphine toxicity, particularly in breastfed infants (deaths reported). FDA 2013: black box warning; codeine contraindicated in children post-tonsillectomy and in breastfeeding mothers; WHO 2013: discouraged in children. Codeine is now largely replaced by alternative analgesics in paediatrics.

The 100,000 Genomes Project
Genomics EnglandA UK government-funded initiative (2012-2018) sequencing 100,000 whole genomes from approximately 85,000 NHS patients and their families — focusing on rare and undiagnosed diseases and cancer. Outcomes: identified diagnostic variants in approximately 25-30% of rare disease patients who had previously been undiagnosed after years of investigation. Built the IT infrastructure, ethical frameworks, clinical pathways and analytical pipelines for NHS genomic medicine. Led to the NHS Genomics Medicine Service (2020) — making WGS available as a clinical service.

OLAPARIB and PARP inhibitors — BRCA in treatment
Oncology/PharmacogenomicsPARP (poly ADP-ribose polymerase) inhibitors exploit a synthetic lethality strategy: BRCA1/2-mutated cancer cells are already deficient in one DNA repair pathway (homologous recombination); PARP inhibitors disable a second pathway (base excision repair) → cancer cells cannot repair DNA → die. Normal cells with intact BRCA function tolerate PARP inhibition. Olaparib (Lynparza): FDA-approved for germline BRCA1/2-mutated ovarian cancer (2014 — first PARP inhibitor); breast cancer (2018); prostate cancer (2020); pancreatic cancer (2019). This "precision lethality" principle uses the tumour's own genetic defect against it.