Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Wanqing Wen^{1

2}, Xiao-Ou Shu³, Xingyi Guo³, Qiuyin Cai³, Jirong Long³, Manjeet K Bolla⁴, Kyriaki Michailidou⁴, Joe Dennis⁴, Qin Wang⁴, Yu-Tang Gao⁵, Ying Zheng⁶, Alison M Dunning⁷, Montserrat García-Closas^{8

9}, Paul Brennan¹⁰, Shou-Tung Chen¹¹, Ji-Yeob Choi^{12

13}, Mikael Hartman^{14

15}, Hidemi Ito¹⁶, Artitaya Lophatananon¹⁷, Keitaro Matsuo¹⁸, Hui Miao¹⁴, Kenneth Muir^{17

19}, Suleeporn Sangrajrang²⁰, Chen-Yang Shen^{21

22}, Soo H Teo^{23

24}, Chiu-Chen Tseng²⁵, Anna H Wu²⁵, Cheng Har Yip²⁴, Jacques Simard²⁶, Paul D P Pharoah^{4

7}, Per Hall²⁷, Daehee Kang²⁸, Yongbing Xiang⁵, Douglas F Easton^{4

7}, Wei Zheng³

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. wanqing.wen@vanderbilt.edu.
² 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.
³ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
⁶ Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
⁷ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁸ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
¹⁰ International Agency for Research on Cancer, Lyon, France.
¹¹ Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
¹² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
¹³ Cancer Research Institute, Seoul National University, Seoul, Korea.
¹⁴ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
¹⁵ Department of Surgery, National University Health System, Singapore, Singapore.
¹⁶ Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁷ Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
¹⁸ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁹ Institute of Population Health, University of Manchester, Manchester, UK.
²⁰ National Cancer Institute, Bangkok, Thailand.
²¹ School of Public Health, China Medical University, Taichung, Taiwan.
²² Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
²³ Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
²⁴ Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
²⁵ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
²⁶ Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
²⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁸ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

PMID: 27931260
PMCID: PMC5146840
DOI: 10.1186/s13058-016-0786-1

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Wanqing Wen et al. Breast Cancer Res. 2016.

. 2016 Dec 8;18(1):124.

doi: 10.1186/s13058-016-0786-1.

Authors

Affiliations

¹ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. wanqing.wen@vanderbilt.edu.
² 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.
³ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
⁶ Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
⁷ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁸ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
⁹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
¹⁰ International Agency for Research on Cancer, Lyon, France.
¹¹ Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
¹² Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
¹³ Cancer Research Institute, Seoul National University, Seoul, Korea.
¹⁴ Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
¹⁵ Department of Surgery, National University Health System, Singapore, Singapore.
¹⁶ Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁷ Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
¹⁸ Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁹ Institute of Population Health, University of Manchester, Manchester, UK.
²⁰ National Cancer Institute, Bangkok, Thailand.
²¹ School of Public Health, China Medical University, Taichung, Taiwan.
²² Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
²³ Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
²⁴ Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
²⁵ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
²⁶ Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
²⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁸ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

PMID: 27931260
PMCID: PMC5146840
DOI: 10.1186/s13058-016-0786-1

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Breast cancer risk; Methodology for SNP data analysis; Prediction model; Statistical methods in genetics.

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Figures

**Fig. 1**
The proportion of cases followed (*PCF*) versus the polygenic risk score (*PRS*) percentile of proportion needed to follow-up (*PNF*). *AUC* area under the receiver operating characteristic curve

See this image and copyright information in PMC

References

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Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Affiliations

Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Authors

Affiliations

Abstract

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References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical