PRSs with traditional risk factors can enhance the accuracy of risk prediction for various cancer types . 10 This approach allows for individualised risk assessment and stratification of cancer screening programs , focusing screening efforts on individuals at highest risk . 11-13 This approach has the potential to enhance cost-effectiveness and reduce the risks associated with false positives and overdiagnosis . 14 , 15 It may also influence decisions regarding the timing of |
In family testing , the PRSs of first-degree family members are correlated , although it is a more complex scenario than monogenic cases where the probability of carrying a variant can be precisely quantified and indicates the need for cascade testing among family members . 21
Pharmacogenomic testing
GPs routinely observe a broad spectrum
of patient responses to medications ,
|
to the first antidepressant trialled . 23 Up to half of this variation in drug response is due to genetic factors . 24 The most commonly prescribed class of antidepressants in primary care are SSRIs . 25 Differences in CYP2D6 genotype can impact response to SSRIs ; 5-10 % of Caucasians are poor metabolisers , while 1-2 % are ultra-rapid metabolisers . 26 Ultra-rapid metabolisers do not respond to SSRIs , and poor metabolisers may experience substantial side effects at |
through several pathology providers but carries out-of-pocket costs in the range of $ 150- $ 200 . Only two tests are currently covered by MBS rebates , and neither is of direct relevance to GP prescribing . 23
Conclusion
The growing evidence of the clinical utility of genomic testing underscores the importance of increasing genetic literacy . PRSs offer promise in assessing the risk
|
Genomic testing holds great promise for assessing and managing an individual ’ s disease and treatment risks . |
||||
screening initiation , screening intervals , |
encompassing both treatment effective- |
standard doses , so may need lower doses . |
of chronic diseases , but clinicians must |
|||||
and the choice of screening tests . Clinical |
ness and potential side effects . Pharma- |
A recent meta-analysis of five clinical tri- |
also upskill to be able to discuss the lim- |
|||||
trials are underway to compare PRS-guided |
cogenomics is a field that explores how |
als showed that patients with pharma- |
itations and clinical implications of the |
|||||
screening with conventional methods for |
genetic distinctions influence these drug |
cogenomic-guided dosing were 1.71 times |
tests with patients . Pharmacogenomic |
|||||
16 , 17 breast and colorectal cancer . |
responses . The aim of pharmacogenom- |
more likely to achieve symptom remission |
testing is a growing area in providing per- |
|||||
|
Limitations and implications
Navigating the evolving landscape of
|
ics is to shift away from a one-size-fits-all and trial-and-error approach towards one that embraces personalised medicine . 1 |
in major depressive disorder than those who received standard care . 27 Evidence in the primary care setting is growing . A case |
sonalised medicine and holds practical relevance in various medical conditions , particularly antidepressant selection . As |
|||||
genetic testing involves understanding |
Notably , more than 98 % of the popu- |
in point , the PRIME Care trial , included |
evidence on utility grows , more tests will |
|||||
the limitations and implications of PRSs . |
lation is likely to carry at least one phar- |
1944 patients with major depressive dis- |
become available , eventually with asso- |
|||||
These scores often rely on genomic data predominantly derived from European populations , which restricts their appli- |
macogenomic variation with practical significance . 1 Most of these variants impact pharmacokinetics , with approx- |
order and showed that pharmacogenomic tests for drug interactions resulted in a significant difference in symptom remis- |
ciated MBS rebates , paving the way for their integration into mainstream general practice . |
|||||
cability and predictive accuracy in other population groups . 8 However , substantial progress is rapidly being made to |
imately 80 % of these genes linked to cytochrome P450 ( CYP ) enzymes . 1 This has clinical significance because indi- |
sion ( 16.5 % vs 11.2 %) at 12 weeks but not at 24 weeks , in those who underwent pharmacogenomic tests versus those who |
References on request from kate . kelso @ adg . com . au |
|||||
increase the applicability of PRSs for all . 18 |
viduals who are categorised as poor or |
received treatment as usual . This indi- |
||||||
In Australia ’ s insurance context , private health insurance is unaffected |
ultrarapid drug metabolisers may need personalised doses to achieve equiva- |
cates that the value of pharmacogenomics may be finding an effective and tolerable |
Online resources |
|||||
by genetic test results as it is not riskrated . 19 , 20 However , life insurance policies and other types of risk-rated insurance , such as disability and income protection insurance , are subject to disclosure requirements outlined in the Insurance Contracts Act of 1984 . 19 , 20 This includes any type of genetic test result , including PRSs . However , a self-imposed moratorium , introduced by the Financial Services Council in 2019 will remain indefinitely , but this comes with specific financial limitations on the level of cover that can be applied for without disclosure |
lent effectiveness or face an elevated risk of adverse drug effects . Testing patients for actionable variants ( meaning cases where a drug – gene interaction test would result in a deviation from the standardof-care drug treatment ) has been shown to reduce clinically significant adverse drug reactions . 22
While pharmacogenomics has been applied to various medication classes and medical conditions , this article focuses on the practical example of antidepressants . Antidepressants are widely used to treat various mental health conditions , how-
|
drug and dose more quickly than employing a trial-and-error approach . 27 A similar trial in Australian general practice is currently underway . 28
Numerous international guidelines are available to facilitate the prescription of pharmacogenomic-led treatments , with many of these resources accessible through the PharmGKB website ( pharmgkb . org ). The RACGP ’ s publication , ‘ Genomics in general practice ,’ offers valuable insights and practical examples of how pharmacogenomics can be applied to a wide range of medications . Pharma-
|
• RACGP guidelines — Genomics in general practice bit . ly / 3HORNdk
• NSW Government — Centre for Genetics Education bit . ly / 4bs5DA2
• Clinical Pharmacogenetics Implementation Consortium — Guidelines cpicpgx . org / guidelines
• NHS England — Genomics Education Programme bit . ly / 3HTjaTu
|
|||||
19 , 20 of any type of genetic testing results . |
ever up to 50 % of patients do not respond |
cogenomic testing is currently available |