Genes are sections of DNA that carry instructions for building proteins, essential for the body’s proper functioning. Changes in these genes are known as single-gene variants. Genetic testing can reveal different types of gene variants, including “pathogenic variants” (or mutations), which disrupt protein function and increase cancer risk. Another category, “variants of uncertain significance” (VUS), has an unclear impact on protein function and cancer risk, requiring further study to understand potential harm. Identifying pathogenic variants provides targeted insights for individual and family screening, prevention, and treatment.
Approximately 5-10% of cancers are hereditary, while the majority develop due to acquired mutations over one’s life. Certain indicators, often termed “red flags,” can signal a hereditary link to cancer, such as a family history with several cases of the same or similar cancers, particularly at younger-than-typical ages. Cancers that appear in multiple generations or affect individuals with rare cancer types may indicate a genetic predisposition. Those of specific backgrounds, like Ashkenazi Jewish heritage, are at increased risk for specific mutations, including BRCA1 and BRCA2, and may benefit from genetic counselling and testing.
Several genes are strongly linked to breast cancer, notably BRCA1 and BRCA2. Mutations in these genes are well-known for raising the risk of both breast and ovarian cancers. Other genes like TP53, CHEK2, PALB2, and ATM also increase breast cancer risk to varying degrees. With advancements in testing, multi-gene panels can screen several genes simultaneously, allowing a broader analysis beyond individual genes like BRCA. Results from these panels can guide decisions on prevention strategies, such as increased monitoring or preventive surgeries, and may influence treatment options if cancer has been diagnosed. Moreover, knowing a family member’s genetic risk can alert close relatives to their potential risk, given that close relatives may have a 50% chance of sharing any pathogenic variant identified.
Polygenic risk scores (PRS) offer a newer method for assessing breast cancer risk by examining the combined effect of numerous small genetic differences, known as single nucleotide polymorphisms (SNPs). Each SNP contributes minimally to risk on its own, but when considered together, they provide a more detailed risk profile. This is particularly helpful for those who lack high-risk mutations but want a personalised assessment due to family history or other concerns. Although PRS is still being incorporated into clinical practice, some testing services now combine PRS with multi-gene panel testing, enhancing the assessment of genetic cancer risk.
A recent example illustrating the impact of PRS involved actress Olivia Munn, who, after initial cancer screenings and genetic testing came back negative, opted for a PRS test. The PRS revealed a 37% lifetime risk of breast cancer, prompting her doctor to recommend a more intensive MRI screening. This MRI led to the discovery of multiple cancer sites, allowing her to pursue timely treatment. Munn credits the PRS with playing a critical role in her cancer detection and care.
If you’re concerned about your cancer risk, speaking with a healthcare provider who understands your personal and family history can help determine the best approach to genetic testing and cancer screening.
Advancements in genetic testing are refining the options available for cancer prevention and treatment, with PRS and multi-gene panels leading the way toward more personalised healthcare. Public awareness, bolstered by stories from high-profile individuals, continues to drive interest in genetic testing, enabling earlier interventions for many.
EDX Medical Group Plc (AQSE:EDX) is a global specialist in digital clinical diagnostics; developing and supporting high-performance products and services to provide cost-effective prediction of disease risk, inform clinical decision-making, enable personalised healthcare and accelerate the development of new medicines for cancer, neurology, heart disease and infectious diseases.
