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Grant Details

Grant Number: 5R01CA089085-05 Interpret this number
Primary Investigator: Olopade, Olufunmilayo
Organization: University Of Chicago
Project Title: Genetics of Breast Cancer in Blacks
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): African Americans and Africans experience a disproportionate burden of pre-menopausal breast cancer for reasons that remain unknown. The identification of persons carrying breast cancer susceptibility genes is a promising approach to understanding the etiology of the disease and developing more effective early detection and prevention strategies. With the cloning of BRCA1 and BRCA2 genes, there is an urgent need to identify mutations among different ethnic populations in order to study mutation spectrum, age-specific penetrance, risks of other cancers, epidemiological risk factors, and effects of modifier genes for mutation carriers. It is more than 6 years since BRCA1was cloned and yet, there is little information available about the role of BRCA1and BRCA2 for ethnic groups other than Caucasians of Northern European ancestry. Our proposal aims to narrow the knowledge gap by examining a large cohort of African American and African breast cancer cases. We propose to ascertain a total of 1000 Nigerian women diagnosed with breast cancer at, or before, age 65, and 1000 controls. All women under the age of 45 and women with a family history of breast or ovarian cancer, or bilateral breast cancer will be screened for BRCA1 and BRCA2 mutations. The incidence and spectrum of mutations identified in these cases will be compared to that previously reported in Caucasian women and to that obtained in 360 African American women from Northern California who are participating in the Cooperative Family Registry for Breast Cancer Studies (CFRBCS). Detailed family cancer history and exposure information will be collected on each participant to determine whether differences exist in exposure history and clustering of breast and other cancers in the families of women with breast cancer, in Nigeria and the United States. Penetrance of BRCA mutations will be estimated for African American and Nigerian kindreds that are segregating a deleterious mutation. UGT1A1 enzyme is one of the major UGT involved in estradiol glucunonidation and also constitutes a major detoxification pathway for toxic or carcinogenic compounds. We have found that populations of African Origin harbor four different alleles of UGT1A1 while non-African populations appear to have only two alleles. In addition, alleles associated with lower gene expression levels reach the highest frequency in populations of sub-Saharan African. Using the resources of the CFRBCS and those collected in this study, the association between single nucleotide polymorphisms and in a number of the genes in the UGTIA cluster and breast cancer will be assessed in a Nigerian case-control study and an African-American case-control study. In addition, UGTIA polymorphisms will be examined as a potential modifies of BRCA1 or BRCA2 cancer risk The accurate definition of genetic risks for young Black women will eventually lead to more accurate clinical risk assessment and the development of targeted prevention, early detection and treatment strategies that should ultimately lead to reduced breast cancer mortality and improved clinical outcomes in young women of African ancestry.

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Publications

A comprehensive examination of breast cancer risk loci in African American women.
Authors: Feng Y, Stram DO, Rhie SK, Millikan RC, Ambrosone CB, John EM, Bernstein L, Zheng W, Olshan AF, Hu JJ, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Press MF, Deming SL, Rodriguez-Gil JL, Palmer JR, Olopade OI, Huo D, Adebamowo CA, Ogundiran T, Chen GK, Stram A, Park K, Rand KA, Chanock SJ, Le Marchand L, Kolonel LN, Conti DV, Easton D, Henderson BE, Haiman CA
Source: Hum Mol Genet, 2014 Oct 15;23(20), p. 5518-26.
EPub date: 2014 May 22.
PMID: 24852375
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Risk factors for pregnancy-associated breast cancer: a report from the Nigerian Breast Cancer Study.
Authors: Hou N, Ogundiran T, Ojengbede O, Morhason-Bello I, Zheng Y, Fackenthal J, Adebamowo C, Anetor I, Akinleye S, Olopade OI, Huo D
Source: Ann Epidemiol, 2013 Sep;23(9), p. 551-7.
EPub date: 2013 Jul 20.
PMID: 23880155
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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 TO, Falusi AG, Nathanson KL, John EM, Hennis AJ, Ambs S, Domchek SM, Rebbeck TR, Simon MS, Nemesure B, Wu SY, Leske MC, Odetunde A, Niu Q, Zhang J, Afolabi C, Gamazon ER, Cox NJ, Olopade CO, Olopade OI, Huo D
Source: Carcinogenesis, 2013 Jul;34(7), p. 1520-8.
EPub date: 2013 Mar 8.
PMID: 23475944
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Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
Authors: Stacey SN, Sulem P, Zanon C, Gudjonsson SA, Thorleifsson G, Helgason A, Jonasdottir A, Besenbacher S, Kostic JP, Fackenthal JD, Huo D, Adebamowo C, Ogundiran T, Olson JE, Fredericksen ZS, Wang X, Look MP, Sieuwerts AM, Martens JW, Pajares I, Garcia-Prats MD, Ramon-Cajal JM, de Juan A, Panadero A, Ortega E, Aben KK, Vermeulen SH, Asadzadeh F, van Engelenburg KC, Margolin S, Shen CY, Wu PE, Försti A, Lenner P, Henriksson R, Johansson R, Enquist K, Hallmans G, Jonsson T, Sigurdsson H, Alexiusdottir K, Gudmundsson J, Sigurdsson A, Frigge ML, Gudmundsson L, Kristjansson K, Halldorsson BV, Styrkarsdottir U, Gulcher JR, Hemminki K, Lindblom A, Kiemeney LA, Mayordomo JI, Foekens JA, Couch FJ, Olopade OI, Gudbjartsson DF, Thorsteinsdottir U, Rafnar T, Johannsson OT, Stefansson K
Source: PLoS Genet, 2010 Jul 22;6(7), p. e1001029.
EPub date: 2010 Jul 22.
PMID: 20661439
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Searching for large genomic rearrangements of the BRCA1 gene in a Nigerian population.
Authors: Zhang J, Fackenthal JD, Huo D, Zheng Y, Olopade OI
Source: Breast Cancer Res Treat, 2010 Nov;124(2), p. 573-7.
EPub date: 2010 Jul 2.
PMID: 20596889
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Advances in breast cancer: pathways to personalized medicine.
Authors: Olopade OI, Grushko TA, Nanda R, Huo D
Source: Clin Cancer Res, 2008 Dec 15;14(24), p. 7988-99.
PMID: 19088015
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MYC in breast tumor progression.
Authors: Chen Y, Olopade OI
Source: Expert Rev Anticancer Ther, 2008 Oct;8(10), p. 1689-98.
PMID: 18925859
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Translational integrity and continuity: personalized biomedical data integration.
Authors: Wang X, Liu L, Fackenthal J, Cummings S, Cook M, Hope K, Silverstein JC, Olopade OI
Source: J Biomed Inform, 2009 Feb;42(1), p. 100-12.
EPub date: 2008 Aug 12.
PMID: 18760382
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Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer.
Authors: Stacey SN, Manolescu A, Sulem P, Thorlacius S, Gudjonsson SA, Jonsson GF, Jakobsdottir M, Bergthorsson JT, Gudmundsson J, Aben KK, Strobbe LJ, Swinkels DW, van Engelenburg KC, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Saez B, Lambea J, Godino J, Polo E, Tres A, Picelli S, Rantala J, Margolin S, Jonsson T, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Sveinsdottir SG, Alexiusdottir K, Saemundsdottir J, Sigurdsson A, Kostic J, Gudmundsson L, Kristjansson K, Masson G, Fackenthal JD, Adebamowo C, Ogundiran T, Olopade OI, Haiman CA, Lindblom A, Mayordomo JI, Kiemeney LA, Gulcher JR, Rafnar T, Thorsteinsdottir U, Johannsson OT, Kong A, Stefansson K
Source: Nat Genet, 2008 Jun;40(6), p. 703-6.
EPub date: 2008 Apr 27.
PMID: 18438407
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Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry.
Authors: Nanda R, Schumm LP, Cummings S, Fackenthal JD, Sveen L, Ademuyiwa F, Cobleigh M, Esserman L, Lindor NM, Neuhausen SL, Olopade OI
Source: JAMA, 2005 Oct 19;294(15), p. 1925-33.
PMID: 16234499
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