Abstract

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

Details

Title
European polygenic risk score for prediction of breast cancer shows similar performance in Asian women
Author
Ho Weang-Kee 1   VIAFID ORCID Logo  ; Min-Min, Tan 1   VIAFID ORCID Logo  ; Mavaddat Nasim 2 ; Mei-Chee, Tai 3 ; Shivaani, Mariapun 1 ; Li, Jingmei 4   VIAFID ORCID Logo  ; Peh-Joo, Ho 5   VIAFID ORCID Logo  ; Dennis, Joe 2   VIAFID ORCID Logo  ; Tyrer, Jonathan P 6   VIAFID ORCID Logo  ; Bolla, Manjeet K 2 ; Michailidou Kyriaki 7 ; Wang, Qin 2 ; Kang Daehee 8 ; Choi Ji-Yeob 9 ; Jamaris Suniza 10 ; Xiao-Ou, Shu 11 ; Sook-Yee, Yoon 3 ; Park, Sue K 8   VIAFID ORCID Logo  ; Sung-Won, Kim 12 ; Chen-Yang, Shen 13 ; Yu Jyh-Cherng 14 ; Tan Ern Yu 15 ; Chan Patrick Mun Yew 15 ; Muir, Kenneth 16   VIAFID ORCID Logo  ; Artitaya, Lophatananon 16 ; Wu, Anna H 17 ; Stram, Daniel O 17   VIAFID ORCID Logo  ; Matsuo Keitaro 18   VIAFID ORCID Logo  ; Ito Hidemi 18   VIAFID ORCID Logo  ; Chan, Ching Wan 19   VIAFID ORCID Logo  ; Ngeow, Joanne 20 ; Yong, Wei Sean 21 ; Lim, Swee Ho 22 ; Lim, Geok Hoon 22   VIAFID ORCID Logo  ; Kwong Ava 23 ; Chan, Tsun L 24 ; Tan, Su Ming 25 ; Seah, Jaime 25 ; John, Esther M 26 ; Kurian, Allison W 27   VIAFID ORCID Logo  ; Koh Woon-Puay 28 ; Khor, Chiea Chuen 5   VIAFID ORCID Logo  ; Iwasaki Motoki 29 ; Yamaji Taiki 29 ; Tan Kiak Mien Veronique 30 ; Tan Kiat Tee Benita 30 ; Spinelli, John J 31 ; Aronson, Kristan J 32 ; Hasan Siti Norhidayu 3 ; Kartini, Rahmat 33   VIAFID ORCID Logo  ; Vijayananthan Anushya 33 ; Sim Xueling 34   VIAFID ORCID Logo  ; Pharoah Paul D P 35   VIAFID ORCID Logo  ; Zheng, Wei 11 ; Dunning, Alison M 36   VIAFID ORCID Logo  ; Simard, Jacques 37   VIAFID ORCID Logo  ; van Dam Rob Martinus 38 ; Cheng-Har, Yip 39   VIAFID ORCID Logo  ; Taib Nur Aishah Mohd 10 ; Hartman, Mikael 40 ; Easton, Douglas F 35   VIAFID ORCID Logo  ; Soo-Hwang, Teo 41   VIAFID ORCID Logo  ; Antoniou, Antonis C 2 

1  University of Nottingham Malaysia, School of Mathematical Sciences, Faculty of Science and Engineering, Semenyih, Malaysia (GRID:grid.440435.2); Cancer Research Malaysia, Subang Jaya, Malaysia (GRID:grid.507182.9) 
2  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
3  Cancer Research Malaysia, Subang Jaya, Malaysia (GRID:grid.507182.9) 
4  Human Genetics, Genome Institute of Singapore, Singapore, Singapore (GRID:grid.418377.e) (ISNI:0000 0004 0620 715X); National University Hospital and NUHS, Department of Surgery, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599) 
5  Human Genetics, Genome Institute of Singapore, Singapore, Singapore (GRID:grid.418377.e) (ISNI:0000 0004 0620 715X) 
6  University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
7  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, Ayios, Cyprus (GRID:grid.417705.0) (ISNI:0000 0004 0609 0940); Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology & Genetics, Ayios, Cyprus (GRID:grid.417705.0) (ISNI:0000 0004 0609 0940) 
8  Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University Graduate School, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
9  Seoul National University Graduate School, Department of Biomedical Sciences, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905); Seoul National University, Cancer Research Institute, Seoul, Korea (GRID:grid.31501.36) (ISNI:0000 0004 0470 5905) 
10  University of Malaya, Jalan Universiti, Department of Surgery, Faculty of Medicine, Kuala Lumpur, Malaysia (GRID:grid.10347.31) (ISNI:0000 0001 2308 5949) 
11  Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
12  Daerim Saint Mary’s Hospital, Department of Surgery, Seoul, Korea (GRID:grid.31501.36) 
13  Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (GRID:grid.482251.8) (ISNI:0000 0004 0633 7958); China Medical University, School of Public Health, Taichung, Taiwan (GRID:grid.254145.3) (ISNI:0000 0001 0083 6092) 
14  Tri-Service General Hospital, Department of Surgery, Taipei, Taiwan (GRID:grid.278244.f) (ISNI:0000 0004 0638 9360) 
15  Tan Tock Seng Hospital, Department of General Surgery, Singapore, Singapore (GRID:grid.240988.f) 
16  The University of Manchester, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407) 
17  University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, USA (GRID:grid.42505.36) (ISNI:0000 0001 2156 6853) 
18  Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan (GRID:grid.410800.d) (ISNI:0000 0001 0722 8444); Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan (GRID:grid.27476.30) (ISNI:0000 0001 0943 978X) 
19  National University of Singapore, Department of Surgery, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University Hospital, National University Health System, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599) 
20  Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745); Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore (GRID:grid.428397.3) (ISNI:0000 0004 0385 0924) 
21  Division of Surgical Oncology, National Cancer Centre, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745) 
22  KK Women’s and Children’s Hospital, Breast Department, Singapore, Singapore (GRID:grid.414963.d) (ISNI:0000 0000 8958 3388) 
23  Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Centre, Happy Valley, Hong Kong (GRID:grid.414963.d); The University of Hong Kong, Department of Surgery, Pok Fu Lam, Hong Kong (GRID:grid.194645.b) (ISNI:0000000121742757); Hong Kong Sanatorium and Hospital, Department of Surgery, Happy Valley, Hong Kong (GRID:grid.194645.b) 
24  Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Centre, Happy Valley, Hong Kong (GRID:grid.194645.b); Hong Kong Sanatorium and Hospital, Department of Pathology, Happy Valley, Hong Kong (GRID:grid.194645.b) 
25  General Surgery, Changi General Hospital, Singapore, Singapore (GRID:grid.413815.a) (ISNI:0000 0004 0469 9373) 
26  Stanford University School of Medicine, Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
27  Stanford University School of Medicine, Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University School of Medicine, Department of Health Research and Policy—Epidemiology, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
28  Health Services and Systems Research, Duke-NUS Medical School, Stanford University School of Medicine, Singapore, Singapore (GRID:grid.428397.3) (ISNI:0000 0004 0385 0924); Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
29  Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan (GRID:grid.272242.3) (ISNI:0000 0001 2168 5385) 
30  Division of Surgical Oncology, National Cancer Centre, Singapore, Singapore (GRID:grid.410724.4) (ISNI:0000 0004 0620 9745); Singapore General Hospital, Department of General Surgery, Singapore, Singapore (GRID:grid.163555.1) (ISNI:0000 0000 9486 5048) 
31  Population Oncology, BC Cancer, 675 West 10th Avenue, Vancouver, Canada (GRID:grid.163555.1); University of British Columbia, School of Population and Public Health, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
32  Queen’s University, Department of Public Health Sciences, and Cancer Research Institute, Kingston, Canada (GRID:grid.410356.5) (ISNI:0000 0004 1936 8331) 
33  University of Malaya, Biomedical Imaging Department, Faculty of Medicine, Kuala Lumpur, Malaysia (GRID:grid.10347.31) (ISNI:0000 0001 2308 5949) 
34  Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
35  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934); University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
36  University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934) 
37  CHU de Québec-Université Laval Research 2705 Blvd Laurier Québec (Québec) G1V 4G2, Genomics Center, Quebec, Canada (GRID:grid.411081.d) (ISNI:0000 0000 9471 1794) 
38  Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431); National University of Singapore, Departments of Medicine, Yong Loo Lin School of Medicine, Singapore, Singapore (GRID:grid.4280.e) (ISNI:0000 0001 2180 6431) 
39  Sime Darby Medical Centre, Subang Jaya, Malaysia (GRID:grid.415921.a) (ISNI:0000 0004 0647 0388) 
40  National University Hospital and NUHS, Department of Surgery, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599) 
41  Cancer Research Malaysia, Subang Jaya, Malaysia (GRID:grid.507182.9); University of Malaya, Jalan Universiti, Department of Surgery, Faculty of Medicine, Kuala Lumpur, Malaysia (GRID:grid.10347.31) (ISNI:0000 0001 2308 5949) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-17680-w
ProQuest document ID
2429349077
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.