Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women
Year: 2023
Type: article
Study design: Observational Study
Abstract: Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
DOI: 10.17615/t87t-nr08
Authors: Hu, D., Conti, D.V., Fejerman, L., Dennis, J., Ambs, S., Yao, S., Pharoah, P.D.P., Gao, G., Olopade, O.I., Ahearn, T.U., Dunning, A.M., Adedokun, B., Ogundiran, T.O., Hu, J.J., The GBHS Study Team, Ojengbede, O., Sandler, D.P., Hennis, A., Haiman, C.A., Olshan, A.F., Easton, D.F., Troester, M.A., Michailidou, K., Bolla, M.K., Garcia-Closas, M., Yarney, J., Taylor, J.A., Fiorica, P.N., Figueroa, J., John, E.M., Wang, Q., Torres-Mejia, G., Nathanson, K.L., Kitahara, C.M., Bensen, J.T., Falusi, A.G., Ziegler, R.G., Ziv, E., Awuah, B., Bandera, E.V., Nemesure, B., Lunetta, K.L., Babalola, C., Ambrosone, C.B., Bernstein, L., Addai-Wiafe, B., Huo, D., Deming-Halverson, S.L., Chanock, S.J., Kushi, L.H., Rodriguez-Gil, J.L., Palmer, J.R., Du, Z., Nyante, S., O’Brien, K.M., Sucheston-Campbell, L.E., Blot, W., Ingles, S.A., Press, M.F., Zirpoli, G., Zheng, W.
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Susan G. Komen for the Cure, Breast Cancer Research Foundation, Kenneth T. and Eileen L. Norris Foundation, Tower Cancer Research Foundation, Andy Hill CARE Fund, Cancer Research UK, European Commission, Ministerio de Economía y Competitividad, National Institutes of Health, U.S. Army, National Cancer Institute, Medical Research and Materiel Command
Awards: G1161123863, G1161922357, G121068745, G1545241092, G1767941747, G1797828594, G1798569254, G2004299919, G2026698695, A GENOME-WIDE BREAST CANCER SCAN IN AFRICAN AMERICANS, G2051375263, G2144275393, G236237718, G2373099447, G2407663899, Breast CAncer STratification: understanding the determinants of risk and prognosis of molecular subtypes, G2453522775, G2461086968, G2486271652, G2539744374, G2646530656, G2675065726, G2694076841, G2703266442, G271288088, G275951588, G3077812842, G3102336106, G3157549237, G3387721620, G3488400535, G3514522626, G3602505857, G3708204173, Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES), G3773105699, G3854560931, G3891343362, G4119534169, G418074593, G4197410787, G4258602497, G434337789, G4407166175, G4470437464, G4562239163, G4592503987, Transcriptome-wide association studies and genetic risk prediction for breast cancer integrating RNA splicing and gene expression from multiple tissues, G4858979163, G4887716027, G4907478063, G495186059, G5045046497, G5052768465, G5111245462, The Nashville Breast Health Study, G5446091787, G5566577447, G5654214539, G5850682332, G585697667, G5955236189, G6229591247, G6272687058, G6289736641, G6343431347, G6402876381, G6871046858, G7238546996, G7242219286, Epidemiology of Breast Cancer Subtypes in African American Women: a Consortium, A Follow-up Study for Causes of Cancer in Black Women, G7446181628, G7501896692, G751661945, G7646998162, G7650865334, G8047235752, G8381382961, G8389391685, Collaborative Oncological Gene-environment Study, G8503433390, G8505307412, G870117454, G8703060161, G880611044, G8820111440, G8854317076, G8867453513, G9000007592, G9000008935, G9000021152, G9000032209, G9000051068, G9000061634, G9000073604, G9000131094, G9000147011, G9000173417, G9000182874, G9000209945, G9000216949, G9000266857, G9000273748, G9000286278, G9000355445, G921773184
OpenAlex ID: W4385889334