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Grant Details

Grant Number: 5R01CA063464-10 Interpret this number
Primary Investigator: Henderson, Brian
Organization: University Of Southern California
Project Title: Genetic Susceptibility to Cancer in Multiethnic Cohorts
Fiscal Year: 2005
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Abstract

Breast and prostate cancers are leading causes of morbidity and mortality caused by a combination of inherited and environmental factors. For the vast majority of these cases, we do not understand the underlying causes, or why different groups have higher rates (e.g. prostate cancer in African Americans). We propose to identify genetic factors that contribute to these cancers by performing well-powered genome-wide association studies, informed by environmental and lifestyle histories collected prospectively in the Multiethnic Cohort (MEC) of African Americans, Latinos, Japanese Americans, Native Hawaiians and Whites n Los Angeles, California and Hawaii. In the previous grant cycle, we established a large repository of DNA and serum and investigated common genetic variation in candidate gene pathways for breast, prostate and colorectal cancer, We developed methods to test genetic variation for association with cancer risk, that now serve as models for the NCI Cohort Consortium and others. In the current cycle, we propose to perform whole-genome association scans of breast and prostate cancer using a two-stage design to identify pan- ethnic genetic variants that affect risk in all five racial-ethnic populations. In stage 1 we will genotype 550,000 single nucleotide polymorphisms (SNPs) in 2,000 breast and 2,000 prostate cancer cases and 4,000 controls. In stage 2 we will perform follow-up genotyping of 4,600 SNPs for each cancer to replicate initial associations in similar numbers of cases and controls. Using the combined stage 1+2 dataset, we will examine interaction between these SNPs and environmental factors and disease severity. These studies will also be designed to identify variants that display strong effects in specific racial-ethnic groups and serve as the initial stage for whole-genome scans in non-White populations. We will also develop a public data enclave to allow access by other investigators to this data. In addition, we propose to establish a population- based repository of tumor specimens from breast and prostate cancer cases in these racial-ethnic groups to be utilized in future studies as relevant molecular classifiers are defined by the Cancer Genome Project. We expect this work to significantly advance knowledge of the etiology of these cancers across these racial- ethnic populations, guiding the development of future preventive, early detection, prognostic and even therapeutic measures.

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Publications

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.
Authors: Agarwal D, Pineda S, Michailidou K, Herranz J, Pita G, Moreno LT, Alonso MR, Dennis J, Wang Q, Bolla MK, Meyer KB, Menéndez-Rodríguez P, Hardisson D, Mendiola M, González-Neira A, Lindblom A, Margolin S, Swerdlow A, Ashworth A, Orr N, Jones M, Matsuo K, Ito H, Iwata H, Kondo N, kConFab Investigators, Australian Ovarian Cancer Study Group, Hartman M, Hui M, Lim WY, Iau PT, Sawyer E, Tomlinson I, Kerin M, Miller N, Kang D, Choi J-, Park SK, Noh D-, Hopper JL, Schmidt DF, Makalic E, Southey MC, Teo SH, Yip CH, Sivanandan K, Tay W-, Brauch H, Brüning T, Hamann U, GENICA Network, Dunning AM, Shah M, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Schmidt MK, Broeks A, Rosenberg EH, van't Veer LJ, Fasching PA, Renner SP, Ekici AB, Beckmann MW, Shen C-, Hsiung C-, Yu J-, Hou M-, Blot W, Cai Q, Wu AH, Tseng C-, Van Den Berg D, Stram DO, Cox A, Brock IW, Reed MW, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Zheng W, Deming-Halverson S, Shrubsole MJ, Long J, Shu X-, Lu W, Gao Y-, Zhang B, Radice P, Peterlongo P, Manoukian S, Mariette F, Sangrajrang S, McKay J, Couch FJ, Toland AE, TNBCC, Yannoukakos D, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Marme F, Burwinkel B, Guénel P, Truong T, Sanchez M, Mulot C, Bojesen SE, Nordestgaard BG, Flyer H, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Mannermaa A, Kataja V, Kosma V-, Hartikainen JM, Lambrechts D, Yesilyurt BT, Floris G, Leunen K, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Wang X, Olson JE, Vachon C, Purrington K, Giles GG, Severi G, Baglietto L, Haiman CA, Henderson BE, Schumacher F, Marchand LL, Simard J, Dumont M, Goldberg MS, Labréche F, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Devilee P, Tollenaar RA, Seynaeve C, García-Closas M, Chanock SJ, Lissowska J, Figueroa JD, Czene K, Eriksson M, Humphreys K, Darabi H, Hooning MJ, Kriege M, Collée JM, Tilanus-Linthorst M, Li J, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Bogdanova N, Dörk T, Hall P, Chenevix-Trench G, Easton DF, Pharroah PD, Arias-Perez JI, Zamora P, Benítez J, Milne RL
Source: Br J Cancer, 2014 Feb 18;110(4), p. 1088-100.
PMID: 24548884
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A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium.
Authors: Milne RL, Herranz J, Michailidou K, Dennis J, Tyrer JP, Zamora MP, Arias-Perez JI, González-Neira A, Pita G, Alonso MR, Wang Q, Bolla MK, Czene K, Eriksson M, Humphreys K, Darabi H, Li J, Anton-Culver H, Neuhausen SL, Ziogas A, Clarke CA, Hopper JL, Dite GS, Apicella C, Southey MC, Chenevix-Trench G, kConFab Investigators, Australian Ovarian Cancer Study Group, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Bojesen SE, Nordestgaard BG, Flyger H, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Wang X, Olson JE, Vachon C, Purrington K, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Dunning AM, Shah M, Guénel P, Truong T, Sanchez M, Mulot C, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, Collée JM, Jager A, Cox A, Brock IW, Reed MW, Devilee P, Tollenaar RA, Seynaeve C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Dumont M, Soucy P, Dörk T, Bogdanova NV, Hamann U, Försti A, Rüdiger T, Ulmer HU, Fasching PA, Häberle L, Ekici AB, Beckmann MW, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Radice P, Peterlongo P, Peissel B, Mariani P, Giles GG, Severi G, Baglietto L, Sawyer E, Tomlinson I, Kerin M, Miller N, Marme F, Burwinkel B, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Lambrechts D, Yesilyurt BT, Floris G, Leunen K, Alnćs GG, Kristensen V, Břrresen-Dale AL, García-Closas M, Chanock SJ, Lissowska J, Figueroa JD, Schmidt MK, Broeks A, Verhoef S, Rutgers EJ, Brauch H, Brüning T, Ko YD, GENICA Network, Couch FJ, Toland AE, TNBCC, Yannoukakos D, Pharoah PD, Hall P, Benítez J, Malats N, Easton DF
Source: Hum Mol Genet, 2014 Apr 1;23(7), p. 1934-46.
EPub date: 2013 Nov 15.
PMID: 24242184
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Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk.
Authors: Wang H, Taverna D, Stram DO, Fortini BK, Cheng I, Wilkens LR, Burnett T, Makar KW, Lindor NM, Hopper JL, Gallinger S, Baron JA, Haile R, Kolonel LN, Henderson BE, Newcomb PA, Casey G, Duggan D, Ulrich CM, Le Marchand L
Source: Cancer Epidemiol Biomarkers Prev, 2013 Nov;22(11), p. 2094-101.
EPub date: 2013 Sep 17.
PMID: 24045924
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Genetic predictors of circulating 25-hydroxyvitamin d and risk of colorectal cancer.
Authors: Hiraki LT, Qu C, Hutter CM, Baron JA, Berndt SI, Bézieau S, Brenner H, Caan BJ, Casey G, Chang-Claude J, Chanock SJ, Conti DV, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hazra A, Henderson B, Hoffmeister M, Hopper JL, Hudson TJ, Jenkins MA, Küry S, Le Marchand L, Lemire M, Ma J, Manson JE, Nan H, Newcomb PA, Ng K, Potter JD, Schoen RE, Schumacher FR, Seminara D, Slattery ML, Wactawski-Wende J, White E, Wu K, Zanke BW, Kraft P, Peters U, Chan AT
Source: Cancer Epidemiol Biomarkers Prev, 2013 Nov;22(11), p. 2037-46.
EPub date: 2013 Aug 27.
PMID: 23983240
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Genome-wide association of body fat distribution in African ancestry populations suggests new loci.
Authors: Liu CT, Monda KL, Taylor KC, Lange L, Demerath EW, Palmas W, Wojczynski MK, Ellis JC, Vitolins MZ, Liu S, Papanicolaou GJ, Irvin MR, Xue L, Griffin PJ, Nalls MA, Adeyemo A, Liu J, Li G, Ruiz-Narvaez EA, Chen WM, Chen F, Henderson BE, Millikan RC, Ambrosone CB, Strom SS, Guo X, Andrews JS, Sun YV, Mosley TH, Yanek LR, Shriner D, Haritunians T, Rotter JI, Speliotes EK, Smith M, Rosenberg L, Mychaleckyj J, Nayak U, Spruill I, Garvey WT, Pettaway C, Nyante S, Bandera EV, Britton AF, Zonderman AB, Rasmussen-Torvik LJ, Chen YD, Ding J, Lohman K, Kritchevsky SB, Zhao W, Peyser PA, Kardia SL, Kabagambe E, Broeckel U, Chen G, Zhou J, Wassertheil-Smoller S, Neuhouser ML, Rampersaud E, Psaty B, Kooperberg C, Manson JE, Kuller LH, Ochs-Balcom HM, Johnson KC, Sucheston L, Ordovas JM, Palmer JR, Haiman CA, McKnight B, Howard BV, Becker DM, Bielak LF, Liu Y, Allison MA, Grant SF, Burke GL, Patel SR, Schreiner PJ, Borecki IB, Evans MK, Taylor H, Sale MM, Howard V, Carlson CS, Rotimi CN, Cushman M, Harris TB, Reiner AP, Cupples LA, North KE, Fox CS
Source: PLoS Genet, 2013;9(8), p. e1003681.
EPub date: 2013 Aug 15.
PMID: 23966867
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SBERIA: set-based gene-environment interaction test for rare and common variants in complex diseases.
Authors: Jiao S, Hsu L, Bézieau S, Brenner H, Chan AT, Chang-Claude J, Le Marchand L, Lemire M, Newcomb PA, Slattery ML, Peters U
Source: Genet Epidemiol, 2013 Jul;37(5), p. 452-64.
EPub date: 2013 May 29.
PMID: 23720162
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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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Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population.
Authors: Haiman CA, Han Y, Feng Y, Xia L, Hsu C, Sheng X, Pooler LC, Patel Y, Kolonel LN, Carter E, Park K, Le Marchand L, Van Den Berg D, Henderson BE, Stram DO
Source: PLoS Genet, 2013 Mar;9(3), p. e1003419.
EPub date: 2013 Mar 28.
PMID: 23555315
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Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk.
Authors: Gaudet MM, Kuchenbaecker KB, Vijai J, Klein RJ, Kirchhoff T, McGuffog L, Barrowdale D, Dunning AM, Lee A, Dennis J, Healey S, Dicks E, Soucy P, Sinilnikova OM, Pankratz VS, Wang X, Eldridge RC, Tessier DC, Vincent D, Bacot F, Hogervorst FB, Peock S, Stoppa-Lyonnet D, KConFab Investigators, Peterlongo P, Schmutzler RK, Nathanson KL, Piedmonte M, Singer CF, Thomassen M, Ontario Cancer Genetics Network, Hansen Tv, Neuhausen SL, Blanco I, Greene MH, Garber J, Weitzel JN, Andrulis IL, Goldgar DE, D'Andrea E, Caldes T, Nevanlinna H, Osorio A, van Rensburg EJ, Arason A, Rennert G, van den Ouweland AM, van der Hout AH, Kets CM, Aalfs CM, Wijnen JT, Ausems MG, HEBON, EMBRACE, Frost D, Ellis S, Fineberg E, Platte R, Evans DG, Jacobs C, Adlard J, Tischkowitz M, Porteous ME, Damiola F, GEMO Study Collaborators, Golmard L, Barjhoux L, Longy M, Belotti M, Ferrer SF, Mazoyer S, Spurdle AB, Manoukian S, Barile M, Genuardi M, Arnold N, Meindl A, Sutter C, Wappenschmidt B, Domchek SM, Pfeiler G, Friedman E, Jensen UB, Robson M, Shah S, Lazaro C, Mai PL, Benitez J, Southey MC, Schmidt MK, Fasching PA, Peto J, Humphreys MK, Wang Q, Michailidou K, Sawyer EJ, Burwinkel B, Guénel P, Bojesen SE, Milne RL, Brenner H, Lochmann M, GENICA Network, Aittomäki K, Dörk T, Margolin S, Mannermaa A, Lambrechts D, Chang-Claude J, Radice P, Giles GG, Haiman CA, Winqvist R, Devillee P, García-Closas M, Schoof N, Hooning MJ, Cox A, Pharoah PD, Jakubowska A, Orr N, González-Neira A, Pita G, Alonso MR, Hall P, Couch FJ, Simard J, Altshuler D, Easton DF, Chenevix-Trench G, Antoniou AC, Offit K
Source: PLoS Genet, 2013;9(3), p. e1003173.
EPub date: 2013 Mar 27.
PMID: 23544012
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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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