Learning about our risk for diseases can be empowering, and there is a growing trend toward this powered by innovations in genetics. Advances in genetics have led to the development of polygenic risk scores (PRS) which provide a more detailed understanding of genetic risk for diseases like breast cancer. But what exactly is a polygenic risk score, and how does it differ from traditional genetic mutations? Let’s break it down.
What is Polygenic Risk?
“Polygenic” means that many genes work together to influence traits or risks. Unlike single-gene mutations that can greatly increase the risk of diseases (such as BRCA1 and BRCA2 mutations in breast cancer), polygenic risk involves many genes, each adding a small amount to the overall risk.
Genetic Mutations vs. Polygenic Risk
Genetic mutations, like those in the BRCA1 or BRCA2 genes, are changes in the DNA that can significantly increase the risk of developing breast cancer. These mutations are rare but carry a high risk for those who have them. Polygenic risk is different. It is based on the combined effect of many common genetic variations called single nucleotide polymorphisms (SNPs). Each SNP might have a tiny impact on breast cancer risk, but when combined, they can provide valuable insights into a person’s overall genetic risk.
In the WISDOM Study, our saliva-based genetic test looks for mutations on the 9 genes associated with significant risk for breast cancer. In addition, we look at over 300 SNPs to identify women at highest risk for hormone negative cancers. (And, as we learn more about which SNPs are associated with breast cancer, we include them in our risk models.) For more information about our genetic test visit our FAQs here.
How Polygenic Risk Scores Are Calculated
Polygenic risk scores are calculated by analyzing a person’s DNA for many SNPs linked to breast cancer. Scientists have found thousands of these SNPs through large studies. By looking at the presence and combination of these SNPs, a polygenic risk score is created. When in combination, some SNPs can be protective against developing disease whereas others can increase the likelihood of developing disease.
The calculation involves:
- Collecting Genetic Data: Usually through a saliva or blood sample.
- Identifying SNPs: Using genetic testing to look for known SNPs linked to breast cancer risk.
- Scoring: Adding up the effects of each SNP to produce a total risk score.
Using Polygenic Risk Scores in Breast Cancer Risk Assessment
Polygenic risk scores are becoming a useful tool in personalized medicine. They offer several benefits:
- Personalized Risk Assessment: PRS provides a detailed picture of genetic risk, helping identify individuals who might need more frequent screening or preventive measures.
- Risk Stratification: PRS helps divide people into different risk categories, allowing for tailored screening and better use of healthcare resources.
- Complementary to Traditional Risk Factors: PRS can be used along with traditional risk factors (like family history and lifestyle) to refine risk estimates and guide clinical decisions.
The WISDOM Study incorporates participants’ Polygenic Risk Score into their personalized Breast Cancer Risk Assessment for a comprehensive understanding of risk.
Relevance to Breast Cancer Risk
Understanding your polygenic risk score can be especially important for people with no known family history of breast cancer or without high-risk genetic mutations. It offers more information that can help with screening and prevention decisions. For example, in WISDOM a person’s polygenic risk score is combined with other risk factors (such as breast density and health history) to determine if she should screen for breast cancer more often, or not. Someone with a low polygenic risk score and no other risk factors might follow standard screening protocols, avoiding unnecessary procedures and worry.
It is important to note, the data traditionally used to create polygenic risk scores only included information from women of European ancestry and therefore performed worse (were less accurate) when used with women of non-European ancestry. WISDOM is one of the first applications of large-scale genetic testing to inform breast cancer risk in all women. One of our goals is to improve the performance (i.e. accuracy) of breast cancer PRS for use in women of diverse, non-European ancestry so that breast cancer risk is more easily and accurately identified, and health disparities can be improved.
In fact, our scientists have already made advancements in genetics that have helped improve PRS models, and they will continue to do so through the next phase of WISDOM. WISDOM’s own Dr. Funmi Olopade from the University of Chicago’s genetic epidemiology studies have advanced our understanding of the burden of breast cancer among young women and those of African descent. Her team recently conducted a genome-wide association study (GWAS) to look for genetic variants that are found more often in participants with breast cancer than in those without. This is believed to be the largest GWAS study to date of breast cancer in this population. The scientists used their findings to create polygenic risk scores (PRS) for breast cancer risk in females of African descent. Results were reported in Nature Genetics on May 13, 2024.
Genetic Testing and Polygenic Risk Scores
Many genetic testing companies now offer polygenic risk scores. These scores can help people understand their genetic risk for breast cancer better. However, it’s important to know that polygenic risk scores are not always accurate and are still being studied and improved upon. Some studies have found that PRSs are not predictive enough to be useful in the clinic because they can result in incorrect or missed information. Therefore, some scientists feel that PRS should be used within the context of research and with professional medical advice. This field is progressing swiftly, and as research continues, the use of PRS in clinical settings will likely become more refined and validated.
Conclusion
WISDOM is investigating the added value of polygenic risk in the context of other known risk factors. We are optimistic that polygenic risk scores tailored by ancestry will provide additional information about each individual’s risk. This can lead to more personalized and effective prevention strategies, improving outcomes for those at risk of breast cancer. To learn more about the scientific advances to polygenic risk scores made in part by our WISDOM experts, read this recent article on gene variants and breast cancer risk in Black women summarizing Dr. Olopade’s work.
If you have any more questions or need further information, feel free to ask our experts by emailing us at wisdomcommunity@ucsf.edu.
