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A genome-wide association study of breast cancer in women of African ancestry

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Abstract

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.

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References

  • Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dork T, Schurmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomaki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M et al (2009) Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41:585–590. doi:10.1038/ng.354

    Article  PubMed  CAS  Google Scholar 

  • Antoniou AC, Wang X, Fredericksen ZS, McGuffog L, Tarrell R, Sinilnikova OM, Healey S, Morrison J, Kartsonaki C, Lesnick T, Ghoussaini M, Barrowdale D, Peock S, Cook M, Oliver C, Frost D, Eccles D, Evans DG, Eeles R, Izatt L, Chu C, Douglas F, Paterson J, Stoppa-Lyonnet D, Houdayer C, Mazoyer S, Giraud S, Lasset C, Remenieras A, Caron O, Hardouin A, Berthet P, Hogervorst FB, Rookus MA, Jager A, van den Ouweland A, Hoogerbrugge N, van der Luijt RB, Meijers-Heijboer H, Gomez Garcia EB, Devilee P, Vreeswijk MP, Lubinski J, Jakubowska A, Gronwald J, Huzarski T, Byrski T, Gorski B, Cybulski C, Spurdle AB, Holland H, Goldgar DE, John EM, Hopper JL, Southey M, Buys SS, Daly MB, Terry MB, Schmutzler RK, Wappenschmidt B, Engel C, Meindl A, Preisler-Adams S, Arnold N, Niederacher D, Sutter C, Domchek SM, Nathanson KL, Rebbeck T, Blum JL, Piedmonte M, Rodriguez GC, Wakeley K, Boggess JF, Basil J, Blank SV, Friedman E, Kaufman B, Laitman Y, Milgrom R, Andrulis IL, Glendon G, Ozcelik H, Kirchhoff T, Vijai J, Gaudet MM, Altshuler D, Guiducci C, Loman N, Harbst K, Rantala J, Ehrencrona H, Gerdes AM, Thomassen M, Sunde L, Peterlongo P, Manoukian S, Bonanni B, Viel A, Radice P et al (2010) A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 42:885–892. doi:10.1038/ng.669

    Article  PubMed  CAS  Google Scholar 

  • Campbell MC, Tishkoff SA (2008) African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 9:403–433. doi:10.1146/annurev.genom.9.081307.164258

    Article  PubMed  CAS  Google Scholar 

  • Chen F, Stram DO, Le Marchand L, Monroe KR, Kolonel LN, Henderson BE, Haiman CA (2010) Caution in generalizing known genetic risk markers for breast cancer across all ethnic/racial populations. Eur J Hum Genet 19:243–245. doi:10.1038/ejhg.2010.185

    Article  PubMed  Google Scholar 

  • 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 (2011) Fine-mapping of breast cancer susceptibility loci characterizes genetic risk in African Americans. Hum Mol Genet 20:4491–4503. doi:10.1093/hmg/ddr367

    Article  PubMed  CAS  Google Scholar 

  • Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schurmann P, Dork T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093. doi:10.1038/nature05887

    Article  PubMed  CAS  Google Scholar 

  • Fletcher O, Johnson N, Orr N, Hosking FJ, Gibson LJ, Walker K, Zelenika D, Gut I, Heath S, Palles C, Coupland B, Broderick P, Schoemaker M, Jones M, Williamson J, Chilcott-Burns S, Tomczyk K, Simpson G, Jacobs KB, Chanock SJ, Hunter DJ, Tomlinson IP, Swerdlow A, Ashworth A, Ross G, dos Santos Silva I, Lathrop M, Houlston RS, Peto J (2011) Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 103:425–435. doi:10.1093/jnci/djq563

    Article  PubMed  CAS  Google Scholar 

  • Ghoussaini M, Fletcher O, Michailidou K, Turnbull C, Schmidt MK, Dicks E, Dennis J, Wang Q, Humphreys MK, Luccarini C, Baynes C, Conroy D, Maranian M, Ahmed S, Driver K, Johnson N, Orr N, dos Santos Silva I, Waisfisz Q, Meijers-Heijboer H, Uitterlinden AG, Rivadeneira F, Hall P, Czene K, Irwanto A, Liu J, Nevanlinna H, Aittomaki K, Blomqvist C, Meindl A, Schmutzler RK, Muller-Myhsok B, Lichtner P, Chang-Claude J, Hein R, Nickels S, Flesch-Janys D, Tsimiklis H, Makalic E, Schmidt D, Bui M, Hopper JL, Apicella C, Park DJ, Southey M, Hunter DJ, Chanock SJ, Broeks A, Verhoef S, Hogervorst FB, Fasching PA, Lux MP, Beckmann MW, Ekici AB, Sawyer E, Tomlinson I, Kerin M, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guenel P, Truong T, Cordina-Duverger E, Menegaux F, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Alonso MR, Gonzalez-Neira A, Benitez J, Anton-Culver H, Ziogas A, Bernstein L, Dur CC, Brenner H, Muller H, Arndt V, Stegmaier C, Justenhoven C, Brauch H, Bruning T, Wang-Gohrke S, Eilber U, Dork T, Schurmann P, Bremer M, Hillemanns P, Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Bermisheva M, Prokofieva D, Khusnutdinova E, Lindblom A, Margolin S, Mannermaa A et al (2012) Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 44:312–318. doi:10.1038/ng.1049

    Article  PubMed  CAS  Google Scholar 

  • Haiman CA, Chen GK, Blot WJ, Strom SS, Berndt SI, Kittles RA, Rybicki BA, Isaacs WB, Ingles SA, Stanford JL, Diver WR, Witte JS, Hsing AW, Nemesure B, Rebbeck TR, Cooney KA, Xu J, Kibel AS, Hu JJ, John EM, Gueye SM, Watya S, Signorello LB, Hayes RB, Wang Z, Yeboah E, Tettey Y, Cai Q, Kolb S, Ostrander EA, Zeigler-Johnson C, Yamamura Y, Neslund-Dudas C, Haslag-Minoff J, Wu W, Thomas V, Allen GO, Murphy A, Chang BL, Zheng SL, Leske MC, Wu SY, Ray AM, Hennis AJ, Thun MJ, Carpten J, Casey G, Carter EN, Duarte ER, Xia LY, Sheng X, Wan P, Pooler LC, Cheng I, Monroe KR, Schumacher F, Le Marchand L, Kolonel LN, Chanock SJ, Berg DV, Stram DO, Henderson BE (2011a) Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21. Nat Genet 43:570–573. doi:10.1038/ng.839

    Article  PubMed  CAS  Google Scholar 

  • Haiman CA, Chen GK, Vachon CM, Canzian F, Dunning A, Millikan RC, Wang X, Ademuyiwa F, Ahmed S, Ambrosone CB, Baglietto L, Balleine R, Bandera EV, Beckmann MW, Berg CD, Bernstein L, Blomqvist C, Blot WJ, Brauch H, Buring JE, Carey LA, Carpenter JE, Chang-Claude J, Chanock SJ, Chasman DI, Clarke CL, Cox A, Cross SS, Deming SL, Diasio RB, Dimopoulos AM, Driver WR, Dunnebier T, Durcan L, Eccles D, Edlund CK, Ekici AB, Fasching PA, Feigelson HS, Flesch-Janys D, Fostira F, Forsti A, Fountzilas G, Gerty SM, Giles GG, Godwin AK, Goodfellow P, Graham N, Greco D, Hamann U, Hankinson SE, Hartmann A, Hein R, Heinz J, Holbrook A, Hoover RN, Hu JJ, Hunter DJ, Ingles SA, Irwanto A, Ivanovich J, John EM, Johnson N, Jukkola-Vuorinen A, Kaaks R, Ko YD, Kolonel LN, Konstantopoulou I, Kosma VM, Kulkarni S, Lambrechts D, Lee AM, Marchand LL, Lesnick T, Liu J, Lindstrom S, Mannermaa A, Margolin S, Martin NG, Miron P, Montgomery GW, Nevanlinna H, Nickels S, Nyante S, Olswold C, Palmer J, Pathak H, Pectasides D, Perou CM, Peto J, Pharoah PD, Pooler LC, Press MF, Pylkas K, Rebbeck TR, Rodriguez-Gil JL, Rosenberg L, Ross E, Rudiger T, Silva Idos S et al (2011b) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43:1210–1214. doi:10.1038/ng.985ng.985

    Article  PubMed  CAS  Google Scholar 

  • Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Huntchinson A, Wang J (2007) A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39:870–874

    Article  PubMed  CAS  Google Scholar 

  • Huo D, Zheng Y, Ogundiran TO, Adebamowo C, Nathanson KL, Domchek SM, Rebbeck TR, Simon MS, John EM, Hennis A, Nemesure B, Wu SY, Leske MC, Ambs S, Niu Q, Zhang J, Cox NJ, Olopade OI (2012) Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry. Carcinogenesis 33:835–840. doi:10.1093/carcin/bgs093

    Article  PubMed  CAS  Google Scholar 

  • Hutter CM, Young AM, Ochs-Balcom HM, Carty CL, Wang T, Chen CT, Rohan TE, Kooperberg C, Peters U (2011) Replication of breast cancer GWAS susceptibility loci in the Women’s Health Initiative African American SHARe Study. Cancer Epidemiol Biomarkers Prev 20:1950–1959. doi:10.1158/1055-9965.EPI-11-0524

    Article  PubMed  CAS  Google Scholar 

  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    Article  PubMed  CAS  Google Scholar 

  • Kim HC, Lee JY, Sung H, Choi JY, Park SK, Lee KM, Kim YJ, Go MJ, Li L, Cho YS, Park M, Kim DJ, Oh JH, Kim JW, Jeon JP, Jeon SY, Min H, Kim HM, Park J, Yoo KY, Noh DY, Ahn SH, Lee MH, Kim SW, Lee JW, Park BW, Park WY, Kim EH, Kim MK, Han W, Lee SA, Matsuo K, Shen CY, Wu PE, Hsiung CN, Kim HL, Han BG, Kang D (2012) A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study. Breast Cancer Res 14:R56. doi:10.1186/bcr3158

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Abecasis GR (2006) Mach 1.0: rapid haplotype reconstruction and missing genotype inference. Am J Hum Genet S79:2290

    Google Scholar 

  • Long J, Cai Q, Sung H, Shi J, Zhang B, Choi JY, Wen W, Delahanty RJ, Lu W, Gao YT, Shen H, Park SK, Chen K, Shen CY, Ren Z, Haiman CA, Matsuo K, Kim MK, Khoo US, Iwasaki M, Zheng Y, Xiang YB, Gu K, Rothman N, Wang W, Hu Z, Liu Y, Yoo KY, Noh DY, Han BG, Lee MH, Zheng H, Zhang L, Wu PE, Shieh YL, Chan SY, Wang S, Xie X, Kim SW, Henderson BE, Le Marchand L, Ito H, Kasuga Y, Ahn SH, Kang HS, Chan KY, Iwata H, Tsugane S, Li C, Shu XO, Kang DH, Zheng W (2012) Genome-wide association study in east Asians identifies novel susceptibility loci for breast cancer. PLoS Genet 8:e1002532. doi:10.1371/journal.pgen.1002532PGENETICS-D-11-01537

    Article  PubMed  CAS  Google Scholar 

  • Meyer KB, Maia AT, O’Reilly M, Teschendorff AE, Chin SF, Caldas C, Ponder BA (2008) Allele-specific up-regulation of FGFR2 increases susceptibility to breast cancer. PLoS Biol 6:e108. doi:10.1371/journal.pbio.0060108

    Article  PubMed  Google Scholar 

  • Pasaniuc B, Zaitlen N, Lettre G, Chen G, Tandon A, Kao L, Ruczinski I, Fornage M, Siscovick D, Zhu X, Larkin E, Lange L (2011) Enhanced statistical tests for GWAS in admixed populations: assessment using African Americans from CARe and a breast cancer consortium (under review)

  • Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 31:33–36. doi:10.1038/ng853ng853

    Article  PubMed  CAS  Google Scholar 

  • Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–9. doi:10.1038/ng1847

    Google Scholar 

  • Price AL, Tandon A, Patterson N, Barnes KC, Rafaels N, Ruczinski I, Beaty TH, Mathias R, Reich D, Myers S (2009) Sensitive detection of chromosomal segments of distinct ancestry in admixed populations. PLoS Genet 5:e1000519. doi:10.1371/journal.pgen.1000519

    Article  PubMed  Google Scholar 

  • Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155:945–959

    PubMed  CAS  Google Scholar 

  • Reed FA, Tishkoff SA (2006) African human diversity, origins and migrations. Curr Opin Genet Dev 16:597–605. doi:10.1016/j.gde.2006.10.008

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Narvaez EA, Rosenberg L, Cozier YC, Cupples LA, Adams-Campbell LL, Palmer JR (2010) Polymorphisms in the TOX3/LOC643714 locus and risk of breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev 19:1320–1327

    Article  PubMed  CAS  Google Scholar 

  • Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ, Albers-Akkers MT, Swinkels DW, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Godino J, Garcia-Prats MD, Polo E, Tres A, Mouy M, Saemundsdottir J, Backman VM, Gudmundsson L, Kristjansson K, Bergthorsson JT, Kostic J, Frigge ML, Geller F, Gudbjartsson D, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Jonsson T, von Holst S, Werelius B, Margolin S, Lindblom A, Mayordomo JI, Haiman CA, Kiemeney LA, Johannsson OT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39:865–869. doi:10.1038/ng2064

    Article  PubMed  CAS  Google Scholar 

  • 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 (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40:703–706. doi:10.1038/ng.131

    Article  PubMed  CAS  Google Scholar 

  • Tarsounas M, Davies AA, West SC (2004) RAD51 localization and activation following DNA damage. Philos Trans R Soc Lond B Biol Sci 359:87–93. doi:10.1098/rstb.2003.1368

    Article  PubMed  CAS  Google Scholar 

  • Tenhagen M, van Diest PJ, Ivanova IA, van der Wall E, van der Groep P (2012) Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets. Endocr Relat Cancer 19:R115–R129. doi:10.1530/ERC-12-0060

    Article  PubMed  CAS  Google Scholar 

  • Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, Cox DG, Hankinson SE, Hutchinson A, Wang Z, Yu K, Chatterjee N, Garcia-Closas M, Gonzalez-Bosquet J, Prokunina-Olsson L, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver R, Prentice R, Jackson R, Kooperberg C, Chlebowski R, Lissowska J, Peplonska B, Brinton LA, Sigurdson A, Doody M, Bhatti P, Alexander BH, Buring J, Lee IM, Vatten LJ, Hveem K, Kumle M, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Chanock SJ, Hunter DJ (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 41:579–584. doi:10.1038/ng.353

    Article  PubMed  CAS  Google Scholar 

  • Turnbull C, Shahana A, Morrison J, Pernet D, Renwick A, Maranian M, Seal S, Ghoussaini M, Hines S, Healey CS, Hughes D (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42:504–507

    Article  PubMed  CAS  Google Scholar 

  • Udler MS, Meyer KB, Pooley KA, Karlins E, Struewing JP, Zhang J, Doody DR, MacArthur S, Tyrer J, Pharoah PD, Luben R, Bernstein L, Kolonel LN, Henderson BE, Le Marchand L, Ursin G, Press MF, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Kang D, Yoo KY, Noh DY, Ahn SH, Ponder BA, Haiman CA, Malone KE, Dunning AM, Ostrander EA, Easton DF (2009) FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation. Hum Mol Genet 18:1692–1703. doi:10.1093/hmg/ddp078

    Article  PubMed  CAS  Google Scholar 

  • Zheng W, Cai Q, Signorello LB, Long J, Hargreaves MK, Deming SL, Li G, Li C, Cui Y, Blot WJ (2009a) Evaluation of 11 breast cancer susceptibility loci in African–American women. Cancer Epidemiol Biomarkers Prev 18:2761–2764. doi:10.1158/1055-9965.EPI-09-0624

    Article  PubMed  CAS  Google Scholar 

  • Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO (2009b) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41:324–328. doi:ng.31810.1038/ng.318

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to CAH [W81XWH-08-1-0383] and the Norris Foundation. Each of the participating studies was supported by the following grants: MEC (National Institutes of Health grants R01-CA63464 and R37-CA54281); CARE (National Institute for Child Health and Development grant NO1-HD-3-3175); WCHS (U.S. Army Medical Research and Material Command (USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health grant R01-CA100598, and the Breast Cancer Research Foundation); SFBCS (National Institutes of Health grant R01-CA77305 and United States Army Medical Research Program grant DAMD17-96-6071); NC-BCFR (National Institutes of Health grant U01-CA69417); CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility National Institute of Environmental Health Sciences, National Institutes of Health, grant number P30-ES10126); PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health); NBHS (National Institutes of Health grant R01-CA100374); SCCS (National Institutes of Health grant R01-CA092447), WFBC (National Institutes of Health grant R01-CA73629); BWHS (National Institutes of Health grants R01-CA58420 and R01-CA98663) and WISE (National Institutes of Health grant P01-CA77596). OI Olopade and D Huo were supported by National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA125183 and National Cancer Institute R01-CA141712. BBCS is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators. 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 BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119,32122, 42107-26, 42129-32, and 44221. Funding for WHI SHARe genotyping was provided by NHLBI Contract N02-HL-64278. We thank the women who volunteered to participate in each study. We also thank Madhavi Eranti, Andrea Holbrook, Paul Poznaik, David Wong and Lucy Xia from the University of Southern California for their technical support. We would also like to acknowledge co-investigators from the WCHS study: Dana H. Bovbjerg (University of Pittsburgh), Lina Jandorf (Mount Sinai School of Medicine) and Gregory Ciupak, Warren Davis, Gary Zirpoli, Song Yao and Michelle Roberts from Roswell Park Cancer Institute.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The experiments done in this manuscript comply with the current laws of the country of USA.

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Fang Chen, Gary K. Chen, Daniel O. Stram, Sue A. Ingles, Suhn K. Rhie, Peggy Wan, Xin Sheng, Loreall C. Pooler, David J. Van Den Berg, Brian E. Henderson & Christopher A. Haiman

  2. Department of Epidemiology, Gillings School of Global Public Health, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    Robert C. Millikan & Sarah Nyante

  3. Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA

    Christine B. Ambrosone

  4. Cancer Prevention Institute of California, Fremont, CA, USA

    Esther M. John

  5. Stanford University School of Medicine, Stanford Cancer Institute, Stanford, CA, USA

    Esther M. John

  6. Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, Duarte, CA, USA

    Leslie Bernstein

  7. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Wei Zheng, Sandra L. Deming, William Blot, Lisa Signorello, Qiuyin Cai, Guoliang Li & Jirong Long

  8. Slone Epidemiology Center at Boston University, Boston, MA, USA

    Julie R. Palmer & Edward A. Ruiz-Narvaez

  9. Department of Epidemiology and Public Health, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

    Jennifer J. Hu & Jorge L. Rodriguez-Gil

  10. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Tim R. Rebbeck, Angela DeMichele, Katherine L. Nathanson & Susan M. Domchek

  11. Epidemiology and Biostatistics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, DC, USA

    Regina G. Ziegler & Stephen J. Chanock

  12. The Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Elisa V. Bandera

  13. Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Michael F. Press

  14. Department of Health Studies, University of Chicago, Chicago, IL, USA

    Dezheng Huo

  15. Department of Medicine, University of Chicago, Chicago, IL, USA

    Yonglan Zheng, Nancy J. Cox & Olufunmilayo I. Olopade

  16. Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Temidayo O. Ogundiran

  17. Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, MD, USA

    Clement Adebamowo

  18. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Michael S. Simon

  19. Chronic Disease Research Centre, Tropical Medicine Research Institute, University of the West Indies, Bridgetown, Barbados

    Anselm Hennis

  20. Department of Preventive Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA

    Anselm Hennis, Barbara Nemesure, Suh-Yuh Wu & M. Cristina Leske

  21. Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA

    Stefan Ambs

  22. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Carolyn M. Hutter, Alicia Young, Charles Kooperberg & Ulrike Peters

  23. Epigenome Center, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    David J. Van Den Berg

  24. Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, HI, USA

    Loic Le Marchand & Laurence N. Kolonel

  25. USC Norris Comprehensive Cancer Center, Harlyne Norris Research Tower, 1450 Biggy Street, Room 1504, Los Angeles, CA, 90033, USA

    Christopher A. Haiman

Authors
  1. Fang Chen
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  2. Gary K. Chen
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  3. Daniel O. Stram
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  4. Robert C. Millikan
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  5. Christine B. Ambrosone
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  6. Esther M. John
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  7. Leslie Bernstein
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  8. Wei Zheng
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  9. Julie R. Palmer
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  10. Jennifer J. Hu
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  13. Sarah Nyante
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  15. Sue A. Ingles
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  17. Edward A. Ruiz-Narvaez
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  24. Qiuyin Cai
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  25. Guoliang Li
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  26. Jirong Long
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  27. Dezheng Huo
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  28. Yonglan Zheng
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  29. Nancy J. Cox
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  30. Olufunmilayo I. Olopade
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  31. Temidayo O. Ogundiran
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  34. Susan M. Domchek
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  35. Michael S. Simon
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  36. Anselm Hennis
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  37. Barbara Nemesure
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  38. Suh-Yuh Wu
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  39. M. Cristina Leske
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  40. Stefan Ambs
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  41. Carolyn M. Hutter
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  42. Alicia Young
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  43. Charles Kooperberg
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  44. Ulrike Peters
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  45. Suhn K. Rhie
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  46. Peggy Wan
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  47. Xin Sheng
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  48. Loreall C. Pooler
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  49. David J. Van Den Berg
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  50. Loic Le Marchand
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  51. Laurence N. Kolonel
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  52. Brian E. Henderson
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  53. Christopher A. Haiman
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Corresponding author

Correspondence to Christopher A. Haiman.

Additional information

F. Chen and G. K. Chen contribued equally to this work.

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Chen, F., Chen, G.K., Stram, D.O. et al. A genome-wide association study of breast cancer in women of African ancestry. Hum Genet 132, 39–48 (2013). https://doi.org/10.1007/s00439-012-1214-y

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  • DOI: https://doi.org/10.1007/s00439-012-1214-y

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