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Grant Details

Grant Number: 1R01CA141712-01 Interpret this number
Primary Investigator: Huo, Dezheng
Organization: University Of Chicago
Project Title: Replication Study of Breast Cancer Susceptibility Genes in Blacks
Fiscal Year: 2009
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Abstract

DESCRIPTION (provided by applicant): African Americans and Africans experience a disproportionate burden of aggressive breast cancer in comparison to all other racial/ethnic groups for reasons that remain unknown and understudied. The paucity of data on the genetic epidemiology of breast cancer for women of African ancestry hinders the development of innovative prevention to reduce health disparities. Because common genetic variants with potential large population attributable risk may play a role in breast cancer development and progression for women of African ancestry in a way different from women of European ancestry, we propose to replicate 5 novel breast cancer susceptibility loci (involving 11 genes) previously identified in genome-wide association studies in a well-characterized cohort of about 2200 breast cancer cases and 2300 controls, all of African ancestry. DNA samples and epidemiologic data for this large study have been collected through Nigerian Breast Cancer Study (Africans), Barbados National Cancer Study (African Barbadians), and the Chicago Breast SPORE and the Breast Cancer Family Registry (African Americans). We will employ the replication plus fine-mapping strategy to genotype exactly same SNPs identified in original studies and a panel of tagSNPs and putative functional variants in these 5 genomic regions. For African Americans, ancestry informative markers will also be genotyped to control for population stratification. Multiple imputation procedure will be used to impute variants that are not genotyped. Logistic regressions will be used to test the associations and calculate odd ratios. Furthermore, we will examine gene-environment interaction as there are sharp contrasts in epidemiologic risk factors among the three populations of African ancestry. This study will advance understanding the genetic risk factors for breast cancer in women of African descent and will be invaluable in developing novel prevention strategies in the future.

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Publications

A comprehensive examination of breast cancer risk loci in African American women.
Authors: Feng Y. , Stram D.O. , Rhie S.K. , Millikan R.C. , Ambrosone C.B. , John E.M. , Bernstein L. , Zheng W. , Olshan A.F. , Hu J.J. , et al. .
Source: Human molecular genetics, 2014-10-15; 23(20), p. 5518-26.
EPub date: 2014-05-22.
PMID: 24852375
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Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.
Authors: Zheng Y. , Ogundiran T.O. , Falusi A.G. , Nathanson K.L. , John E.M. , Hennis A.J. , Ambs S. , Domchek S.M. , Rebbeck T.R. , Simon M.S. , et al. .
Source: Carcinogenesis, 2013 Jul; 34(7), p. 1520-8.
EPub date: 2013-03-08.
PMID: 23475944
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda K.L. , Chen G.K. , Taylor K.C. , Palmer C. , Edwards T.L. , Lange L.A. , Ng M.C. , Adeyemo A.A. , Allison M.A. , Bielak L.F. , et al. .
Source: Nature genetics, 2013 Jun; 45(6), p. 690-6.
EPub date: 2013-04-14.
PMID: 23583978
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A genome-wide association study of breast cancer in women of African ancestry.
Authors: Chen F. , Chen G.K. , Stram D.O. , Millikan R.C. , Ambrosone C.B. , John E.M. , Bernstein L. , Zheng W. , Palmer J.R. , Hu J.J. , et al. .
Source: Human genetics, 2013 Jan; 132(1), p. 39-48.
EPub date: 2012-08-25.
PMID: 22923054
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Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry.
Authors: Huo D. , Zheng Y. , Ogundiran T.O. , Adebamowo C. , Nathanson K.L. , Domchek S.M. , Rebbeck T.R. , Simon M.S. , John E.M. , Hennis A. , et al. .
Source: Carcinogenesis, 2012 Apr; 33(4), p. 835-40.
EPub date: 2012-02-22.
PMID: 22357627
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Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.
Authors: Hou N. , Zheng Y. , Gamazon E.R. , Ogundiran T.O. , Adebamowo C. , Nathanson K.L. , Domchek S.M. , Rebbeck T.R. , Simon M.S. , John E.M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012 Mar; 21(3), p. 552-6.
EPub date: 2012-01-11.
PMID: 22237986
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Novel germline PALB2 truncating mutations in African American breast cancer patients.
Authors: Zheng Y. , Zhang J. , Niu Q. , Huo D. , Olopade O.I. .
Source: Cancer, 2012-03-01; 118(5), p. 1362-70.
EPub date: 2011-08-26.
PMID: 21932393
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Lack of association between common single nucleotide polymorphisms in the TERT-CLPTM1L locus and breast cancer in women of African ancestry.
Authors: Zheng Y. , Ogundiran T.O. , Adebamowo C. , Nathanson K.L. , Domchek S.M. , Rebbeck T.R. , Simon M.S. , John E.M. , Hennis A. , Nemesure B. , et al. .
Source: Breast cancer research and treatment, 2012 Feb; 132(1), p. 341-5.
EPub date: 2011-11-29.
PMID: 22134622
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Germline mutational analysis of the C19orf62 gene in African-American women with breast cancer.
Authors: Zheng Y. , Zhang J. , Niu Q. , Olopade O.I. , Huo D. .
Source: Breast cancer research and treatment, 2011 Jun; 127(3), p. 871-7.
EPub date: 2011-03-24.
PMID: 21431873
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