7 August 2020
A ground-breaking genetic study in Asian women led by Malaysian scientists in collaboration with Singapore and the University of Cambridge revealed that a genetics tool developed to help European women assess breast cancer risk also works in Asian women.
The tool, called a Polygenic Risk Score (PRS), separates people into different risk groups based on their genetic sequence, to predict their future risk of developing breast cancer. The results can empower women to decide which screening and prevention is right for them, and help reduce inefficiency, unnecessary cost, and even possible harm caused by over-diagnosis.
“This is the first large study of the PRS in an Asian population. Previously, Asian studies were nearly six times smaller than studies in European women, and due to lack of data in Asians, it was unclear if PRSs are effective in predicting breast cancer risk in non-European women. Through the significant increase in data from Malaysia and Singapore, we now know PRS can help us identify more accurately who is at high risk of breast cancer. Our results suggest that only 30% of Malaysian and Singaporean women have a predicted risk similar to that of European women, and that using the PRS accurately identifies these high-risk women,” said Professor Datin Paduka Dr Teo Soo Hwang, OBE, Chief Scientific Officer at Cancer Research Malaysia and co-lead of the project.
The collaborative study, published in the prestigious Nature Communications science journal, was the result of a collaboration between Cancer Research Malaysia and Associate Professor Ho Weang Kee, University of Nottingham; Professor Douglas Easton and Professor Antonis Antoniou, University of Cambridge, UK; Professor Nur Aishah Mohd Taib, Universiti Malaya; Professor Dato’ Dr Yip Cheng Har, Subang Jaya Medical Centre; Associate Professor Mikael Hartman, National University Health System, Dr Li Jingmei, Genome Institute of Singapore, and six hospitals in Singapore; and a large population-based prospective cohort from Singapore.
“Combining genetic factors into one comprehensive model is critical to move from the research to a tool for women to use. We evaluated the PRS in 45,212 Asian women, from Singapore, Malaysia, Japan, Korea, China, Hong Kong, Thailand, Taiwan, USA, and Canada. Studies such as these require large sample sizes, and so, bringing together patients from University Malaya, Subang Jaya Medical Centre, National University Hospital, Singapore, and six other major treatment centres in Singapore really gave us the sample size to be able to evaluate the tool in Asians,” said Associate Professor Ho Weang Kee, first author of the study.
“Our study is a critical piece of the puzzle that helps us better understand breast cancer risks in different women around the world. There are differences in the genetic make-up of Asian women compared to women of European descent, which means their propensity to develop breast cancer may be different. Understanding this can help us to work out why some women are at higher risk of the disease, which in turn should help us to improve screening, prevention and ultimately treatment of the disease,” said Professor Douglas Easton, Director of the Centre for Cancer Genetic Epidemiology, University of Cambridge, and co-lead of the study.
“We have been developing a model for predicting breast cancer risk in European women that includes the PRS and this is now approved for clinical use. This study is the first big step towards enabling the use of such tools in the clinical management of women of Asian ancestry,” said Professor Antonis Antoniou, University of Cambridge, and co-lead of the study.
Women are generally recommended to start screening at age 50. However, in most Asian countries, many women who could be at risk of breast cancer do not go for screening. This leads to late detection and a lower survival rate.
“The Polygenic Risk Score is an important step forward and lays the foundation for risk-based mammography screening in Singapore,” said Associate Professor Mikael Hartman, National University Health System, Singapore.
“Risk-based screening may be particularly important in low- and middle-resource countries that do not have population-based screening, such as Malaysia. Without the funding for population-based screening, identifying individuals with higher risk may be an important strategy for early detection,” said Professor Nur Aishah Mohd Taib, Universiti Malaya Cancer Research Institute, Malaysia.
There is an urgent need to develop an appropriate screening strategy for Asian women. Malaysia anticipates a 49% increase in breast cancer cases from 2012 to 2025. Malaysia has a much lower five-year survival rate compared to other Asian countries at only 63%, whereas South Korea is at 92% and Singapore is at 80%.
“Research collaborations like this are extremely important, bringing together data and expertise from the UK and Malaysia to help find solutions to one of the world’s leading causes of death – cancer,” said His Excellency Charles Hay MVO, British High Commissioner to Malaysia.
The study was supported by numerous research grants and charitable funding, principally from the Medical Research Council and Academy of Sciences Malaysia via the Newton-Ungku Omar Fund, the Wellcome Trust Collaborative Science Award, Yayasan Sime Darby, Yayasan PETRONAS, and Estee Lauder Group of Companies.