Journal article

Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Xiang Shu, Jirong Long, Qiuyin Cai, Sun-Seog Kweon, Ji-Yeob Choi, Michiaki Kubo, Sue K Park, Manjeet K Bolla, Joe Dennis, Qin Wang, Yaohua Yang, Jiajun Shi, Xingyi Guo, Bingshan Li, Ran Tao, Kristan J Aronson, Kelvin YK Chan, Tsun L Chan, Yu-Tang Gao, Mikael Hartman Show all

Nature Communications | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for ..

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Grants

Awarded by US National Institutes of Health


Awarded by Department of Defense Idea Awards


Awarded by Vanderbilt-Ingram Cancer Center


Awarded by BRL (Basic Research Laboratory) program through the National Research Foundation of Korea - Ministry of Education, Science and Technology


Awarded by National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea


Awarded by National Research Foundation of Korea - Ministry of Education, Science and Technology


Awarded by Biobank of Chonnam National University Hwasun Hospital


Awarded by Ministry of Education, Culture, Sports, Science, and Technology of Japan


Awarded by Hospitalbased Epidemiologic Research Program at Aichi Cancer Center from the Japanese Ministry of Education, Culture, Sports, Science and Technology


Awarded by Japan Agency for Medical Research and development, AMED


Awarded by Asia Cancer Program (CRUK)


Awarded by Canadian Cancer Society


Awarded by Los Angeles County Asian-American Breast Cancer Case-Control Study (California Breast Cancer Research Program)


Awarded by National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program


Awarded by Malaysian Ministry of Higher Education


Awarded by Northern California Breast Cancer Family Registry (National Cancer Institute [USA])


Awarded by Biomedical Research Council


Awarded by Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project [NIH]


Awarded by Cancer Research UK


Awarded by European Community


Funding Acknowledgements

The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agents. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was supported in part by the US National Institutes of Health grants R01CA124558, R01CA148667, R01CA158473, R01CA064277, R37CA070867, and UM1CA182910 (to W.Z.); R01CA118229 and R01CA092585 (to X.-O.S.); R01CA122756 (to Q.C.); and R01CA137013 (to J. Long), Department of Defense Idea Awards BC011118 (to X.-O.S.) and BC050791 (to Q.C.), and Ingram and Anne Potter Wilson Professorship and Research Reward funds (to W.Z.). Sample preparation and genotyping assays at Vanderbilt were conducted at the Survey and Biospecimen Shared Resources and Vanderbilt Microarray Shared Resource, which are supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485). Data analyses were conducted using the Advanced Computing Center for Research and Education (ACCRE) at Vanderbilt University. The SeBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011-0001564). KOHBRA/KOGES was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (#1020350). Studies conducted among Asian women include (Principal Investigator, grant support): the Shanghai Breast Cancer Study (W.Z. and X.-O.S., R01CA064277), the Shanghai Women's Health Study (W. Z., R37CA070867 and UM1CA182910), the Shanghai Breast Cancer Survival Study (X.-O. S., R01CA118229), the Shanghai Endometrial Cancer Study (X.-O.S., R01CA092585, controls only), the Seoul Breast Cancer Study [D.K., BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347)], the BioBank Japan Project (S.-K.L., the Ministry of Education, Culture, Sports, Sciences and Technology from the Japanese Government); the Hwasun Cancer Epidemiology Study-Breast (S.-S.K., the Biobank of Chonnam National University Hwasun Hospital, a member of the Korea Biobank Network, #07SA2014020), the Nagano Breast Cancer Study (M.I., Grants-in-Aid for the Third Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas, 17015049 and for Scientific Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan), the Hospitalbased Epidemiologic Research Program at Aichi Cancer Center [Grant-in-Aid for Scientific Research on Priority Areas of Cancer (No. 17015018) from the Japanese Ministry of Education, Culture, Sports, Science and Technology and the "Practical Research for Innovative Cancer Control (15ck0106177h0001)" from the Japan Agency for Medical Research and development, AMED (K. Matsuo), and Cancer Bio Bank Aichi; the Asia Cancer Program (K. Muir and A.L., the NIHR Manchester Biomedical Research Centre and by the ICEP and CRUK, #C18281/A19169); the Canadian Breast Cancer Study (K.A. and J. Spinelli, the Canadian Cancer Society, #313404); the Los Angeles County Asian-American Breast Cancer Case-Control Study (A.H.W., the California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-0018, 10PB0098].Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403); the Malaysian Breast Cancer Genetic Study (S.-H.T., the Malaysian Ministry of Higher Education [UM. C/HlR/MOHE/06] and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education [RP046B15HTM]); the Northern California Breast Cancer Family Registry (E.M. J., the National Cancer Institute [USA, UM1 CA164920]. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR.); the Singapore Breast Cancer Cohort (M.H., the NUS start-up Grant, National University Cancer Institute Singapore [NCIS] Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort [SCCSMEC], which was funded by the Biomedical Research Council, grant number: 05/1/21/19/425); and the Taiwanese Breast Cancer Study (C.-Y.S., the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan). Studies conducted among European-ancestry women Genotyping of the OncoArray was principally funded by three sources: the PERSPECTIVE project, funded from the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec, and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project [NIH Grants U19 CA148065, X01HG007492]; and Cancer Research UK [C1287/A10118, C1287/A16563]. The BCAC is funded by Cancer Research UK [C1287/A16563], the European Community's Seventh Framework Programme under grant agreement 223175 [HEALTH-F22009-223175] (COGS).