Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction.
About this Publication
Title
Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction.
Pubmed ID
38741014
(View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat Genet. 2024 May 13
Authors
Jia G, Ping J, Guo X, Yang Y, Tao R, Li B, Ambs S, Barnard ME, Chen Y, Garcia-Closas M, Gu J, Hu JJ, Huo D, John EM, Li CI, Li JL, Nathanson KL, Nemesure B, Olopade OI, Pal T, ...show more Press MF, Sanderson M, Sandler DP, Shu XO, Troester MA, Yao S, Adejumo PO, Ahearn T, Brewster AM, Hennis AJM, Makumbi T, Ndom P, O'Brien KM, Olshan AF, Oluwasanu MM, Reid S, Butler EN, Huang M, Ntekim A, Qian H, Zhang H, Ambrosone CB, Cai Q, Long J, Palmer JR, Haiman CA, Zheng W
Affiliations
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
- Laboratory of Human Carcinogenesis, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
- Slone Epidemiology Center, Boston University, Boston, MA, USA.
- Division of Epidemiology, Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA.
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
- Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Public Health Sciences, University of Miami School of Medicine, Miami, FL, USA.
- Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.
- Departments of Epidemiology & Population Health and of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University, New York, NY, USA.
- Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL, USA.
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
- Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
- Department of Epidemiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, USA.
- Department of Nursing, College of Medicine, University of Ibadan, Ibadan, Nigeria.
- Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- George Alleyne Chronic Disease Research Centre, University of the West Indies, Bridgetown, Barbados.
- Department of Surgery, Mulago Hospital, Kampala, Uganda.
- Yaounde General Hospital, Yaounde, Cameroon.
- Department of Health Promotion and Education, College of Medicine, University of Ibadan, Ibadan, Nigeria.
- Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Radiation Oncology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
- Department of Statistics and Operation Research, University of North Carolina, Chapel Hill, NC, USA.
- Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. wei.zheng@vanderbilt.edu.
Abstract
We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.
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