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Genetic sequencing has significantly advanced our ability to detect individuals at increased risk of developing specific conditions and to identify diseases in their earliest stages. Predictive genetic testing can reveal susceptibilities to conditions like cancer, while diagnostic testing enables the detection of diseases before symptoms arise. These tools offer the potential for more personalized and effective healthcare. However, with these advancements come important considerations around accessibility, ethics, and practical implementation. This blog will explore how genetic testing is shaping the future of early disease detection and the essential need for equitable access to these critical technologies.
Risk and early disease detection
One of the most significant outcomes of genetic sequencing is the ability to detect individuals at increased risk of developing specific conditions (predictive genetic testing), as well as enhancing the ability of healthcare practitioners to identify the presence of disease in its early stages (diagnostic genetic testing).
For example, women who carry specific genetic variants in the BRCA1 and BRCA2 genes are at a significantly increased risk of developing breast or ovarian cancer during their lifetime – up to an 85% lifetime risk in cases of breast cancer and up to a 63% lifetime risk in ovarian cancer. This is a dramatic difference compared to those who do not carry a mutation, who have an overall breast cancer risk of approximately 15%. As a result, a number of countries including Australia, the US, UK, France, Germany and Sweden, offer BRCA1 and BRCA2 testing to people who are born female with a family history of breast or ovarian cancer. This enables early risk detection and the implementation of personalized prevention strategies prior to disease development.
However, it’s important to note that availability and accessibility of testing can vary dramatically between countries, healthcare systems, and regions where factors such as insurance coverage come into play (we will explore these in greater depth later in this paper). For example, in Italy BRCA testing isn’t free of charge in all regions and there is significant variation in testing practices across the country.
Another method of assessing disease risk is through the use of polygenic risk scores, an innovative approach in genetic research that measures an individual's predisposition to certain diseases based on their genetic makeup. Derived from genome-wide association studies (GWAS), PRS aggregate the effects of numerous genetic variants to give an individual an overall “score” to estimate their likelihood of developing a disease. While PRS cannot definitively predict if someone will develop a disease, they provide an estimate of genetic risk. These scores can be integrated with health and lifestyle data to further enhance risk prediction.
The benefits of PRS include early intervention and personalized treatment plans. By identifying individuals at higher genetic risk, clinicians can implement early lifestyle changes and tailor pharmacotherapy to improve treatment outcomes. However, integrating PRS into clinical practice raises ethical and practical concerns. Patients need to be informed about the limitations of PRS, and genetic counseling may be necessary. Data privacy and security are crucial, and equitable access to PRS testing must be ensured, as most scores are currently based on populations with European ancestry, which may not be accurate for other ethnic backgrounds.
For example, PRS holds immense potential in predicting the risk of developing liver diseases like metabolic dysfunction-associated steatohepatitis (MASH). Unlike traditional risk factors, such as obesity and insulin resistance, which offer a general risk assessment, PRS provides a personalized risk profile based on genetic predisposition. One example can be found in a 2021 study from Biaco et al., which looked at hepatocellular carcinoma (a type of liver cancer) risk in individuals with dysmetabolism and non-alcoholic fatty liver disease (NAFLD, now known as metabolic dysfunction-associated steatotic liver disease or MASLD). Researchers developed PRS using genetic variants from genes like PNPLA3, TM6SF2, MBOAT7, and GCKR, and analyzed their impact on HCC development. Utilizing data from the NAFLD cohort and UK Biobank, they found that these PRS could help identify individuals at high risk for HCC, regardless of the presence of significant liver scarring (a common indicator of advanced liver disease).
Overall, PRS offer significant potential for early disease detection and improving disease management, but careful consideration of ethical, practical, and accessibility issues is essential for their successful integration into healthcare.
Scaling: From family history screening to population testing
Historically, costs and limited access to sequencing technologies have led many genetic screening programs, including those used to identify individuals with risk variants in BRCA genes, to take a family history-based approach. In practice this means only offering sequencing to individuals with a clear family history of a condition. However, research shows that basing testing on family history alone is not necessarily an effective method for identifying the majority of at-risk patients.
A 2015 cost-effectiveness analysis of population screening for BRCA mutations in Ashkenazi Jewish women living in the UK (who are more likely to carry risk variants than the general population) found that over 50% of carriers in this demographic were missed when using a family history-based approach. The analysis estimated that, based on the available data, a population level BRCA screening could lead to 276 fewer ovarian cancer cases and 508 fewer breast cancer cases if there was a 71% testing uptake. Significantly, this indicated that population-scale testing would not only save lives and reduce incidents of cancer, but was estimated to save the National Health Service £3.7 million at the time of publication.
With the development of targeted treatments and interventions only set to grow, integrating genetic testing into healthcare has never been more important in order to connect patients with breakthrough treatments that can dramatically alter the course of their health and lives.
For more information, download our whitepaper on genetic testing as a public health initiative:
