title: Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry.
abstract: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.
  
  
  
  We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.
  
  
  
  We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P < 0.05. Compared with women in the middle quintile of the PRS, women in the top 1% group had a 2.70-fold elevated risk of breast cancer (95% CI: 2.15-3.40). The risk prediction model with the PRS had an area under the receiver operating characteristic curve of 0.606. The lifetime risk of breast cancer for Shanghai Chinese women in the lowest and highest 1% of the PRS was 1.35% and 10.06%, respectively.
  
  
  
  Approximately one-half of GWAS-identified breast cancer risk variants can be directly replicated in East Asian women. Collectively, common genetic variants are important predictors for breast cancer risk. Using common genetic variants for breast cancer could help identify women at high risk of breast cancer.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. wanqing.wen@vanderbilt.edu.|Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA. wanqing.wen@vanderbilt.edu.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Wen
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Guo
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Jirong
authors.initials: J
authors.lastname: Long
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Manjeet K
authors.initials: MK
authors.lastname: Bolla
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Michailidou
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Dennis
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.affiliation: Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.|Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Closas
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Shou-Tung
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.|Department of Surgery, National University Health System, Singapore, Singapore.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hartman
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
authors.forename: Artitaya
authors.initials: A
authors.lastname: Lophatananon
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.affiliation: Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.|Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.affiliation: National Cancer Institute, Bangkok, Thailand.
authors.forename: Suleeporn
authors.initials: S
authors.lastname: Sangrajrang
authors.affiliation: School of Public Health, China Medical University, Taichung, Taiwan.|Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.affiliation: Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.|Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Soo H
authors.initials: SH
authors.lastname: Teo
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Chiu-Chen
authors.initials: CC
authors.lastname: Tseng
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Cheng Har
authors.initials: CH
authors.lastname: Yip
authors.affiliation: Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.|Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.|Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000465:Algorithms; D001208:Asia / Q000453:epidemiology; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015233:Models, Statistical; D016017:Odds Ratio; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors
keywords: Breast cancer risk; Methodology for SNP data analysis; Prediction model; Statistical methods in genetics