Study Improves Accuracy for Breast Cancer Genetic Markers in Ashkenazi Jewish Women
A new study by researchers in the UK and Israel has investigated how to improve breast cancer genetic tests for Ashkenazi Jewish women. By analysing genetic samples from women from Ashkenazi Jewish backgrounds, they were able to correctly adjust the risk estimates from commercially available genetic screening tests, giving a more accurate result. They detail their technique in the journal Genetics in Medicine.
New forms of genetic tests can tell women their personal risk of developing breast cancer. However, previous research has shown they are not accurate for many Black, Asian or Ashkenazi Jewish women, or women with a mixed ethnic background.
The study focuses on tiny genetic variations called Single Nucleotide Polymorphisms (SNPs) – which, depending on the unique combination of them, can increase or decrease the risk of breast cancer.
This information is used to produce a Polygenic Risk Score (PRS), which can inform women whether they are at low, average, or high risk of developing breast cancer in the next 10 years. PRS are becoming more widely available through commercial companies and research studies on the NHS breast screening programme.
Current PRSs were developed from large-scale genome studies which predominantly collected genetic data from mainstream White European populations. As a result, the accuracy of a PRS for an individual will depend on how closely their genetic material resemble those of the people whose data was used to develop the risk score.
This means that while commercially available PRS can accurately predict breast cancer risk for mainstream White European women, they often exaggerate this risk for Black, Asian or Ashkenazi Jewish women, or women with a mixed ethnic background.
In this new study, researchers compared two available PRS based on two SNPs – SNP142 and the commercial SNP78 – and analysed their accuracy for women of Ashkenazi Jewish ancestry.
The findings showed that these PRS tests inaccurately predicted Ashkenazi Jewish women to be at higher risk of developing breast cancer.
After adjusting the test for Ashkenazi Jewish ancestry, the researchers were able to generate a more accurate prediction of breast cancer risk for these women.
The research team used genetic information from Ashkenazi Jewish women in both Manchester and Israel, with data from the Predicting the Risk of Cancer at Screening (PROCAS) study conducted in Greater Manchester, a Manchester regional genetics database, and the Breast Cancer in Northern Israel (BCINIS) study.
This research was led by Professor Gareth Evans, a leading expert in breast cancer genetics and SNPs testing and NIHR Manchester BRC Cancer Prevention and Early Detection Theme Lead.
Professor Evans said: “Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have great potential to improve personalised screening methods. However, it is clear from our findings that you cannot simply apply current PRS developed using genetic data from individuals of white European ancestry to those from Ashkenazi Jewish backgrounds.
“A test result which exaggerates a woman’s risk of the disease could lead to undue stress or concern and unnecessary screening and preventative measures that they don’t need. Future PRS for Ashkenazi Jewish women should be based on their genetic data to provide a more accurate risk prediction.
“This study is an important step forward in our continued research into breast cancer genetic testing for people of different ethnic backgrounds to improve equity. More accurate and personalised PRS are required to avoid further increasing health inequalities and so patients can receive high-quality screening, care, and treatments.”
Source: University of Manchester
