46 CLINICAL FOCUS
46 CLINICAL FOCUS
14 MARCH 2025 ausdoc . com . au
| THE | VACCINE AND PREVENTION SPECIAL
Therapy Update
Genomics and the GP
General practice
Dr Sibel Saya is an academic genetic counsellor and postdoctoral research fellow with the department of general practice and primary care , and the Centre for Cancer Research at the University of Melbourne . Dr Saya has an interest in the implementation of new genetic and genomic tests in general practice .
Dr Brent Venning is a GP and PhD candidate with the department of general practice and primary care at the University of Melbourne . Dr Venning has research interests in cancer screening , diagnosis and the role of genomics in primary care .
In this rapidly expanding field , the assessment of polygenic risk scores and pharmacogenomics are two areas that show promise for boosting provision of personalised medicine in primary care .
NEED TO KNOW
Genomic testing involves the assessment of information across multiple genes to provide information about an individual ’ s health .
Polygenic risk scores are genomic tests which predict an individual ’ s risk of common diseases , such as heart disease , type 2 diabetes , mental health disorders and cancer .
Pharmacogenomics is a genomic test which predicts an individual ’ s metabolism of certain medications and can direct drug and dose choice .
As the evidence for the clinical utility of genomic tests in primary care grows , GPs will be required to facilitate informed decision-making for their patients and to interpret results of such tests .
GENOMIC testing describes the assessment of genetic information across multiple genes , all of which , together or separately , can provide information about an individual ’ s health . Genomic testing may be useful in both diagnostic and predictive settings . The gradual adoption of genomic testing in clinical practice contrasts with the growing significance and popularity of direct-to-consumer genomic testing among the general population . This highlights the imperative to boost genetic literacy within primary care . 1 This is particularly important as patients prefer the active involvement of their GPs in genomic testing . 2-6 A guide to the many different types of genomic tests that may be available to and applicable in the general practice setting is available ( see online resources ). This article focuses on emerging areas of genomic testing relevant to the future of general practice , with specific attention to polygenic risk score tests and pharmacogenomics .
Polygenic risk scores
GPs frequently evaluate patients ’ risk of chronic disease in their daily clinical practice . This assessment typically considers factors like age , gender , ethnicity , lifestyle choices ( such as weight , smoking , alcohol use and exercise ), clinical measurements ( such as blood pressure
and biomarkers ), environmental factors , and family history . For example , GPs routinely conduct risk assessments for conditions such as cardiovascular disease , guiding the prescription of antihypertensives or lipid-lowering therapies . Similarly , for common cancers , they recommend routine , early or more intensive cancer screening based on risk evaluations . Despite genomic testing not currently being part of individual risk assessment , this emerging field holds great promise in advancing our understanding of an individual ’ s disease susceptibility , and subsequent management of their risk . 7
Polygenic risk scores ( PRSs ) test for the presence of hundreds of common genomic variants , each associated with a small increased risk of a particular disease . In contrast to single gene or monogenic tests , where disease-causing variants are very rare , a PRS can provide personalised risk information for any individual in the population . Table 1 shows how the two types of tests differ , using the example of single gene / monogenic predisposition
This emerging field holds great promise in advancing our understanding of an individual ’ s disease susceptibility .
versus PRSs for breast cancer .
PRSs have been developed for multiple complex conditions , including heart disease , type 2 diabetes , mental health disorders and cancer . 7 , 8 The potential clinical utility of a PRS extends beyond individuals with significant family histories , offering valuable information to the entire population . Given the established management of risk for common diseases in primary care , implementing PRSs in general practice is a logical and practical choice . For illustrative purposes , this article will explore the application of PRSs in the context of cardiovascular disease and cancer , although they have been developed for various medical conditions .
Cardiovascular disease
PRSs consistently demonstrate predictive value in various cardiovascular scenarios . In the context of coronary artery disease , they can facilitate early identification of individuals who might benefit from lifestyle modification and statins , enabling timely initiation of pharmacotherapies and enhancing risk stratification , particularly for patients with intermediate 10-year atherosclerotic cardiovascular disease risk . 9 PRSs also play a role in identifying individuals at high risk of AF , allowing for screening , early detection and subsequent anticoagulation . 9 Furthermore , LDL cholesterol PRSs can reliably predict LDL levels , even in cases of severe hypercholesterolaemia , potentially influencing the selection and dose of LDL-lowering medications . 9
Cancer
There is growing interest in using PRSs to improve cancer risk assessment for personalised prevention and screening . Combining
Table 1 . Monogenic versus polygenic risk scores for breast cancer
How many variants impact risk ?
Single gene / monogenic predisposition to cancer eg , BRCA1 or BRCA2 for breast cancer
One disease-causing variant in the gene increases risk 5-7-fold
Genomic risk prediction for cancer eg , polygenic risk score for breast cancer
Hundreds of common variants each associated with small increases in risk
How common are they ?
< 1 % of the population carry a disease-causing variant
Are applicable to anyone in the population , as each variant is common
Risk increase |
5-7-fold |
90 % of the population will have a |
|
|
≤2-fold risk increase |
Implications for family members
Testing usually indicated
Testing done
All first-degree relatives have a 50 % chance of carrying the variant
In families with multiple cancers or people with certain types of cancer
In familial cancer centres with pre-test counselling , or oncology services
Risk is spread across hundreds of variants , so implications for family members are minimal
Applicable to anyone
Possibly in primary care , although not standard practice yet