Malaysian scientists in collaboration with Singapore and the University of Cambridge have successfully developed a genetic tool to assess breast cancer risk for Asian women.
The tool, called a Polygenic Risk Score (PRS), can be used to predict the likelihood a woman will develop breast cancer based on her genetic sequence. The subsequent 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.
“Individualised screening and prevention of breast cancer is important because the majority of Asian women have a low risk of developing breast cancer, and only a small proportion have inherited genetic factors that are associated with an increased risk to the disease. We have now developed a genetic tool to accurately determine a woman’s risk of breast cancer, enabling Asians to achieve greater equity in access to technology, and pave the way to reducing the gap in survival of cancer in Asians compared to Europeans,” 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 Genetics in Medicine 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; Professor Wei Zheng, Vanderbilt University; Associate Professor Mikael Hartman, National University Health System, Dr Li Jingmei, Genome Institute of Singapore, and six hospitals in Singapore; as well as three large population-based prospective cohorts from Singapore, Korea and China.
“The development of an accurate tool for Asian women requires large sample sizes. Unfortunately, the majority of research studies have been on European women, and the resultant tools are less accurate on Asian women. Our study brought together 58,760 women from Malaysia, Singapore, Japan, Korea, China, Hong Kong, Thailand, Taiwan, USA and Canada thus, gave us the sample size to identify genetic markers that are important for Asian populations. This is also the first breast cancer study to adopt multi-ancestry development methods, to gain accuracy by integrating data from 228,951 European women with Asian-specific genetic markers. Our results show that these methods significantly improve the accuracy of the tool,” said Associate Professor Dr Ho Weang Kee, joint first author of the study.
“The genetic make-up is not the same for all Asians. For example, the genetic architecture of Malay, Chinese and Indian women are very different from each other. Bringing together patients from University Malaya, Subang Jaya Medical Centre, National University Hospital, Singapore, and six other major treatment centres in Singapore has significantly increased the sample size of Southeast Asians and had enabled us to show that the new Asian tool is predictive of breast cancer risk across the Malay, Chinese and Indian ethnic groups from Malaysia and Singapore,” said Dr Tai Mei Chee, joint first author 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 Asian 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%.
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.