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Grant Details

Grant Number: 7R01CA073629-10 Interpret this number
Primary Investigator: Hu, Jennifer
Organization: University Of Miami School Of Medicine
Project Title: Molecular Epidemiology and Prevention of Breast Cancer
Fiscal Year: 2006
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Abstract

DESCRIPTION (provided by applicant): Breast cancer is the most common cancer among women excluding skin cancers. Considerable evidence associated DNA damage/repair with breast cancer risk; however, conducting a large population screening for every cancer susceptibility gene (e.g., DNA repair) is not yet feasible, and it is still not clear to what extent DNA repair genetic variants contribute to repair function and breast cancer risk. To provide more effective etiology-based strategies for cancer prevention, our long-term objectives are: (i) to evaluate the genetic regulation of DNA damage/repair in breast cancer susceptibility; (ii) to identify high-risk populations by using validated DNA damage/repair markers; and (iii) to reduce breast cancer risk in genetically susceptible (sub)populations through effective intervention. To achieve our long-term goals, the proposed study's primary objective is to test the working hypothesis that amino acid substitution variants of DNA repair genes impede repair function, elevate DNA damage, and increase risk of breast cancer. Since multiple DNA repair pathways are required to maintain genome integrity, and many genes are involved in different repair pathways, genetic defects in multiple DNA repair genes may have additive or multiplicative effects on repair functions and human breast cancer risk. Therefore, genotypes and phenotypes in different repair pathways must be evaluated simultaneously in order to fully assess their impact on breast cancer susceptibility. Our secondary objective is to test whether concurrent germ line single nucleotide polymorphisms (SNPs) in base excision repair (BER), nucleotide excision repair (NER), and double-strand break/recombination repair (DSB/RR) have additive or multiplicative effects on breast cancer risk. We propose to expand our parent breast cancer case-control study to 800 cases and 800 controls (frequency-matched to cases by race and age [+/- 5 yrs]) in order to assess gene-gene interactions in breast cancer risk. A baseline questionnaire will collect information on established breast cancer risk factors. Genomic DNA will be used for genotyping assays. Peripheral lymphocytes will be used for four DNA damage/repair functional assays. The multidisciplinary research team is already in place for the research. We believe this proposed research will advance our knowledge of genetic susceptibility to breast cancer and targets for prevention. This information can be translated into health behavior promotion because genetically susceptible (sub)populations are more motivated for screening and intervention.

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Publications

Combined genetic and nutritional risk models of triple negative breast cancer.
Authors: Lee E, Levine EA, Franco VI, Allen GO, Gong F, Zhang Y, Hu JJ
Source: Nutr Cancer, 2014;66(6), p. 955-63.
EPub date: 2014 Jul 14.
PMID: 25023197
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Genome-wide association study of age at menarche in African-American women.
Authors: Demerath EW, Liu CT, Franceschini N, Chen G, Palmer JR, Smith EN, Chen CT, Ambrosone CB, Arnold AM, Bandera EV, Berenson GS, Bernstein L, Britton A, Cappola AR, Carlson CS, Chanock SJ, Chen W, Chen Z, Deming SL, Elks CE, Evans MK, Gajdos Z, Henderson BE, Hu JJ, Ingles S, John EM, Kerr KF, Kolonel LN, Le Marchand L, Lu X, Millikan RC, Musani SK, Nock NL, North K, Nyante S, Press MF, Rodriquez-Gil JL, Ruiz-Narvaez EA, Schork NJ, Srinivasan SR, Woods NF, Zheng W, Ziegler RG, Zonderman A, Heiss G, Gwen Windham B, Wellons M, Murray SS, Nalls M, Pastinen T, Rajkovic A, Hirschhorn J, Adrienne Cupples L, Kooperberg C, Murabito JM, Haiman CA
Source: Hum Mol Genet, 2013 Aug 15;22(16), p. 3329-46.
EPub date: 2013 Apr 17.
PMID: 23599027
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A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry.
Authors: Monda KL, Chen GK, Taylor KC, Palmer C, Edwards TL, Lange LA, Ng MC, Adeyemo AA, Allison MA, Bielak LF, Chen G, Graff M, Irvin MR, Rhie SK, Li G, Liu Y, Liu Y, Lu Y, Nalls MA, Sun YV, Wojczynski MK, Yanek LR, Aldrich MC, Ademola A, Amos CI, Bandera EV, Bock CH, Britton A, Broeckel U, Cai Q, Caporaso NE, Carlson CS, Carpten J, Casey G, Chen WM, Chen F, Chen YD, Chiang CW, Coetzee GA, Demerath E, Deming-Halverson SL, Driver RW, Dubbert P, Feitosa MF, Feng Y, Freedman BI, Gillanders EM, Gottesman O, Guo X, Haritunians T, Harris T, Harris CC, Hennis AJ, Hernandez DG, McNeill LH, Howard TD, Howard BV, Howard VJ, Johnson KC, Kang SJ, Keating BJ, Kolb S, Kuller LH, Kutlar A, Langefeld CD, Lettre G, Lohman K, Lotay V, Lyon H, Manson JE, Maixner W, Meng YA, Monroe KR, Morhason-Bello I, Murphy AB, Mychaleckyj JC, Nadukuru R, Nathanson KL, Nayak U, N'diaye A, Nemesure B, Wu SY, Leske MC, Neslund-Dudas C, Neuhouser M, Nyante S, Ochs-Balcom H, Ogunniyi A, Ogundiran TO, Ojengbede O, Olopade OI, Palmer JR, Ruiz-Narvaez EA, Palmer ND, Press MF, Rampersaud E, Rasmussen-Torvik LJ, Rodriguez-Gil JL, Salako B, Schadt EE, Schwartz AG, Shriner DA, Siscovick D, Smith SB, Wassertheil-Smoller S, Speliotes EK, Spitz MR, Sucheston L, Taylor H, Tayo BO, Tucker MA, Van Den Berg DJ, Edwards DR, Wang Z, Wiencke JK, Winkler TW, Witte JS, Wrensch M, Wu X, Yang JJ, Levin AM, Young TR, Zakai NA, Cushman M, Zanetti KA, Zhao JH, Zhao W, Zheng Y, Zhou J, Ziegler RG, Zmuda JM, Fernandes JK, Gilkeson GS, Kamen DL, Hunt KJ, Spruill IJ, Ambrosone CB, Ambs S, Arnett DK, Atwood L, Becker DM, Berndt SI, Bernstein L, Blot WJ, Borecki IB, Bottinger EP, Bowden DW, Burke G, Chanock SJ, Cooper RS, Ding J, Duggan D, Evans MK, Fox C, Garvey WT, Bradfield JP, Hakonarson H, Grant SF, Hsing A, Chu L, Hu JJ, Huo D, Ingles SA, John EM, Jordan JM, Kabagambe EK, Kardia SL, Kittles RA, Goodman PJ, Klein EA, Kolonel LN, Le Marchand L, Liu S, McKnight B, Millikan RC, Mosley TH, Padhukasahasram B, Williams LK, Patel SR, Peters U, Pettaway CA, Peyser PA, Psaty BM, Redline S, Rotimi CN, Rybicki BA, Sale MM, Schreiner PJ, Signorello LB, Singleton AB, Stanford JL, Strom SS, Thun MJ, Vitolins M, Zheng W, Moore JH, Williams SM, Ketkar S, Zhu X, Zonderman AB, NABEC Consortium, UKBEC Consortium, BioBank Japan Project, AGEN Consortium, Kooperberg C, Papanicolaou GJ, Henderson BE, Reiner AP, Hirschhorn JN, Loos RJ, North KE, Haiman CA
Source: Nat Genet, 2013 Jun;45(6), p. 690-6.
EPub date: 2013 Apr 14.
PMID: 23583978
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A genome-wide scan for breast cancer risk haplotypes among African American women.
Authors: Song C, Chen GK, Millikan RC, Ambrosone CB, John EM, Bernstein L, Zheng W, Hu JJ, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Press MF, Deming SL, Rodriguez-Gil JL, Chanock SJ, Wan P, Sheng X, Pooler LC, Van Den Berg DJ, Le Marchand L, Kolonel LN, Henderson BE, Haiman CA, Stram DO
Source: PLoS One, 2013;8(2), p. e57298.
EPub date: 2013 Feb 28.
PMID: 23468962
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A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.
Authors: Siddiq A, Couch FJ, Chen GK, Lindström S, Eccles D, Millikan RC, Michailidou K, Stram DO, Beckmann L, Rhie SK, Ambrosone CB, Aittomäki K, Amiano P, Apicella C, Australian Breast Cancer Tissue Bank Investigators, Baglietto L, Bandera EV, Beckmann MW, Berg CD, Bernstein L, Blomqvist C, Brauch H, Brinton L, Bui QM, Buring JE, Buys SS, Campa D, Carpenter JE, Chasman DI, Chang-Claude J, Chen C, Clavel-Chapelon F, Cox A, Cross SS, Czene K, Deming SL, Diasio RB, Diver WR, Dunning AM, Durcan L, Ekici AB, Fasching PA, Familial Breast Cancer Study, Feigelson HS, Fejerman L, Figueroa JD, Fletcher O, Flesch-Janys D, Gaudet MM, GENICA Consortium, Gerty SM, Rodriguez-Gil JL, Giles GG, van Gils CH, Godwin AK, Graham N, Greco D, Hall P, Hankinson SE, Hartmann A, Hein R, Heinz J, Hoover RN, Hopper JL, Hu JJ, Huntsman S, Ingles SA, Irwanto A, Isaacs C, Jacobs KB, John EM, Justenhoven C, Kaaks R, Kolonel LN, Coetzee GA, Lathrop M, Le Marchand L, Lee AM, Lee IM, Lesnick T, Lichtner P, Liu J, Lund E, Makalic E, Martin NG, McLean CA, Meijers-Heijboer H, Meindl A, Miron P, Monroe KR, Montgomery GW, Müller-Myhsok B, Nickels S, Nyante SJ, Olswold C, Overvad K, Palli D, Park DJ, Palmer JR, Pathak H, Peto J, Pharoah P, Rahman N, Rivadeneira F, Schmidt DF, Schmutzler RK, Slager S, Southey MC, Stevens KN, Sinn HP, Press MF, Ross E, Riboli E, Ridker PM, Schumacher FR, Severi G, Dos Santos Silva I, Stone J, Sund M, Tapper WJ, Thun MJ, Travis RC, Turnbull C, Uitterlinden AG, Waisfisz Q, Wang X, Wang Z, Weaver J, Schulz-Wendtland R, Wilkens LR, Van Den Berg D, Zheng W, Ziegler RG, Ziv E, Nevanlinna H, Easton DF, Hunter DJ, Henderson BE, Chanock SJ, Garcia-Closas M, Kraft P, Haiman CA, Vachon CM
Source: Hum Mol Genet, 2012 Dec 15;21(24), p. 5373-84.
EPub date: 2012 Sep 13.
PMID: 22976474
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A genome-wide association study of breast cancer in women of African ancestry.
Authors: Chen F, Chen GK, Stram DO, Millikan RC, Ambrosone CB, John EM, Bernstein L, Zheng W, Palmer JR, Hu JJ, Rebbeck TR, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Press MF, Ruiz-Narvaez EA, Deming SL, Rodriguez-Gil JL, Demichele A, Chanock SJ, Blot W, Signorello L, Cai Q, Li G, Long J, Huo D, Zheng Y, Cox NJ, Olopade OI, Ogundiran TO, Adebamowo C, Nathanson KL, Domchek SM, Simon MS, Hennis A, Nemesure B, Wu SY, Leske MC, Ambs S, Hutter CM, Young A, Kooperberg C, Peters U, Rhie SK, Wan P, Sheng X, Pooler LC, Van Den Berg DJ, Le Marchand L, Kolonel LN, Henderson BE, Haiman CA
Source: Hum Genet, 2013 Jan;132(1), p. 39-48.
EPub date: 2012 Aug 25.
PMID: 22923054
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Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans.
Authors: Chen F, Chen GK, Millikan RC, John EM, Ambrosone CB, Bernstein L, Zheng W, Hu JJ, Ziegler RG, Deming SL, Bandera EV, Nyante S, Palmer JR, Rebbeck TR, Ingles SA, Press MF, Rodriguez-Gil JL, Chanock SJ, Le Marchand L, Kolonel LN, Henderson BE, Stram DO, Haiman CA
Source: Hum Mol Genet, 2011 Nov 15;20(22), p. 4491-503.
EPub date: 2011 Aug 18.
PMID: 21852243
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The landscape of recombination in African Americans.
Authors: Hinch AG, Tandon A, Patterson N, Song Y, Rohland N, Palmer CD, Chen GK, Wang K, Buxbaum SG, Akylbekova EL, Aldrich MC, Ambrosone CB, Amos C, Bandera EV, Berndt SI, Bernstein L, Blot WJ, Bock CH, Boerwinkle E, Cai Q, Caporaso N, Casey G, Cupples LA, Deming SL, Diver WR, Divers J, Fornage M, Gillanders EM, Glessner J, Harris CC, Hu JJ, Ingles SA, Isaacs W, John EM, Kao WH, Keating B, Kittles RA, Kolonel LN, Larkin E, Le Marchand L, McNeill LH, Millikan RC, Murphy A, Musani S, Neslund-Dudas C, Nyante S, Papanicolaou GJ, Press MF, Psaty BM, Reiner AP, Rich SS, Rodriguez-Gil JL, Rotter JI, Rybicki BA, Schwartz AG, Signorello LB, Spitz M, Strom SS, Thun MJ, Tucker MA, Wang Z, Wiencke JK, Witte JS, Wrensch M, Wu X, Yamamura Y, Zanetti KA, Zheng W, Ziegler RG, Zhu X, Redline S, Hirschhorn JN, Henderson BE, Taylor HA Jr, Price AL, Hakonarson H, Chanock SJ, Haiman CA, Wilson JG, Reich D, Myers SR
Source: Nature, 2011 Jul 20;476(7359), p. 170-5.
EPub date: 2011 Jul 20.
PMID: 21775986
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Genetic polymorphisms of multiple DNA repair pathways impact age at diagnosis and TP53 mutations in breast cancer.
Authors: Smith TR, Liu-Mares W, Van Emburgh BO, Levine EA, Allen GO, Hill JW, Reis IM, Kresty LA, Pegram MD, Miller MS, Hu JJ
Source: Carcinogenesis, 2011 Sep;32(9), p. 1354-60.
EPub date: 2011 Jun 23.
PMID: 21700777
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Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a Breast Cancer Consortium.
Authors: Pasaniuc B, Zaitlen N, Lettre G, Chen GK, Tandon A, Kao WH, Ruczinski I, Fornage M, Siscovick DS, Zhu X, Larkin E, Lange LA, Cupples LA, Yang Q, Akylbekova EL, Musani SK, Divers J, Mychaleckyj J, Li M, Papanicolaou GJ, Millikan RC, Ambrosone CB, John EM, Bernstein L, Zheng W, Hu JJ, Ziegler RG, Nyante SJ, Bandera EV, Ingles SA, Press MF, Chanock SJ, Deming SL, Rodriguez-Gil JL, Palmer CD, Buxbaum S, Ekunwe L, Hirschhorn JN, Henderson BE, Myers S, Haiman CA, Reich D, Patterson N, Wilson JG, Price AL
Source: PLoS Genet, 2011 Apr;7(4), p. e1001371.
EPub date: 2011 Apr 21.
PMID: 21541012
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The potential for enhancing the power of genetic association studies in African Americans through the reuse of existing genotype data.
Authors: Chen GK, Millikan RC, John EM, Ambrosone CB, Bernstein L, Zheng W, Hu JJ, Chanock SJ, Ziegler RG, Bandera EV, Henderson BE, Haiman CA, Stram DO
Source: PLoS Genet, 2010 Sep 2;6(9), p. e1001096.
EPub date: 2010 Sep 2.
PMID: 20824062
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Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk.
Authors: Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ
Source: Carcinogenesis, 2008 Nov;29(11), p. 2132-8.
EPub date: 2008 Aug 13.
PMID: 18701435
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Comparison of multivariate adaptive regression splines and logistic regression in detecting SNP-SNP interactions and their application in prostate cancer.
Authors: Lin HY, Wang W, Liu YH, Soong SJ, York TP, Myers L, Hu JJ
Source: J Hum Genet, 2008;53(9), p. 802-11.
EPub date: 2008 Jul 8.
PMID: 18607530
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OGG1 is degraded by calpain following oxidative stress and cisplatin exposure.
Authors: Hill JW, Hu JJ, Evans MK
Source: DNA Repair (Amst), 2008 Apr 2;7(4), p. 648-54.
EPub date: 2008 Feb 21.
PMID: 18294929
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Polymorphisms in drug metabolism genes, smoking, and p53 mutations in breast cancer.
Authors: Van Emburgh BO, Hu JJ, Levine EA, Mosley LJ, Case LD, Lin HY, Knight SN, Perrier ND, Rubin P, Sherrill GB, Shaw CS, Carey LA, Sawyer LR, Allen GO, Milikowski C, Willingham MC, Miller MS
Source: Mol Carcinog, 2008 Feb;47(2), p. 88-99.
PMID: 17683074
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DNA-repair genetic polymorphisms and breast cancer risk.
Authors: Smith TR, Levine EA, Perrier ND, Miller MS, Freimanis RI, Lohman K, Case LD, Xu J, Mohrenweiser HW, Hu JJ
Source: Cancer Epidemiol Biomarkers Prev, 2003 Nov;12(11 Pt 1), p. 1200-4.
PMID: 14652281
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Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer.
Authors: Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ
Source: Cancer Lett, 2003 Feb 20;190(2), p. 183-90.
PMID: 12565173
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Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity.
Authors: Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD
Source: Carcinogenesis, 2001 Jun;22(6), p. 917-22.
PMID: 11375899
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Alpha-tocopherol dietary supplement decreases titers of antibody against 5-hydroxymethyl-2'-deoxyuridine (HMdU).
Authors: Hu JJ, Chi CX, Frenkel K, Smith BN, Henfelt JJ, Berwick M, Mahabir S, D'Agostino RB Jr
Source: Cancer Epidemiol Biomarkers Prev, 1999 Aug;8(8), p. 693-8.
PMID: 10744129
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