Improving personalised screening, treatment, and care through Polygenic Risk Scores.

Personalising care and treatments is central to Manchester BRC’s precision medicine approach – allowing our doctors and researchers to predict which treatments or prevention strategies work best for individual patients.

Polygenic Risk Scores (PRS) use large amounts of data on tiny genetic variations across a population to tell a person’s risk of developing diseases such as cancer and arthritis. Manchester BRC has a wealth of expertise using PRS across large-scale clinical trials and data sciences.

In breast cancer screening, PRS is testing personalised ‘risk scores’ on their likelihood of women developing the disease in the next decade. This informs them if they are at low, average, or high risk of breast cancer, and is also investigating whether those at low risk can safely attend screening less often, while high risk women are offered more frequent check-ups.

This project is a collaboration between researchers and clinicians across Manchester BRC and supported by the charity Prevent Breast Cancer. Building on the PROCAS and current BC-Predict trials, new research led by Professor Gareth Evans, Theme Lead for Cancer PED, is looking at how to make PRS more accurate for women from Black and Minority Ethnic (BAME) communities.

“The move towards Polygenic Risk Scores and personalised breast cancer screening is massively promising. However, a limitation of current scores on high-risk cancer genes is that they use data based mainly on white European women, so may not be suitable for those from BAME groups.

He said: “The move towards Polygenic Risk Scores and personalised breast cancer screening is massively promising. However, a limitation of current scores on high-risk cancer genes is that they use data based mainly on white European women, so may not be suitable for those from BAME groups.

“Our latest research looked at data from the PROCAS study, high-risk cancer genes, and tiny genetic variants many of us carry which slightly raise or lower our cancer risk. We found that when applied to women from black, Asian and Jewish backgrounds, current PRS inaccurately predicted many women to be at higher risk of breast cancer.

“Care needs to be taken in applying PRS across the whole population. They urgently need to be improved for screening BAME women, and we are currently working on developing more accurate PRS so that they can receive safe, high-quality screening, care and treatment.”

Alongside this, our Musculoskeletal theme are using PRS to improve treatment selection in conditions such as inflammatory arthritis – led by Andrew Morris, Professor of Statistical Genetics, together with Stephen Eyre, Professor of Complex Disease Genetics, and Magnus Rattray, Professor of Computational and Systems Biology.

A recent award from the Medical Research Council (MRC) / NIHR Methodology Research Programme will allow the development of new methods to integrate different layers of omics data to better understand how genetic variants impact on disease. By understanding which biological pathways are most important in the development of these conditions, we can potentially use the patient’s own genetics and ‘partitioned’ PRS to personalise treatments.

Professor Morris is also sponsor for three international fellowships (Wellcome Trust and Japan Society for the Promotion of Science) investigating the transferability of PRS across population groups and the interplay of lifestyle risk factors and genetics on the predictive performance of PRS.