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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

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A.
Authors: Wang H, Burnett T, Kono S, Haiman CA, Iwasaki M, Wilkens LR, Loo LW, Van Den Berg D, Kolonel LN, Henderson BE, Keku TO, Sandler RS, Signorello LB, Blot WJ, Newcomb PA, Pande M, Amos CI, West DW, Bézieau S, Berndt SI, Zanke BW, Hsu L, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Lindor NM, Haile RW, Hopper JL, Jenkins MA, Gallinger S, Casey G, Colon Cancer Family Registry (CCFR), Stenzel SL, Schumacher FR, Peters U, Gruber SB, Colorectal Transdisciplinary Study (CORECT), Tsugane S, Stram DO, Le Marchand L
Source: Nat Commun, 2014 Aug 8;5, p. 4613.
EPub date: 2014 Aug 8.
PMID: 25105248
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Gene-environment interaction involving recently identified colorectal cancer susceptibility Loci.
Authors: Kantor ED, Hutter CM, Minnier J, Berndt SI, Brenner H, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Cotterchio M, Du M, Duggan D, Fuchs CS, Giovannucci EL, Gong J, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Jenkins MA, Jiao S, Kolonel LN, Le Marchand L, Lemire M, Ma J, Newcomb PA, Ochs-Balcom HM, Pflugeisen BM, Potter JD, Rudolph A, Schoen RE, Seminara D, Slattery ML, Stelling DL, Thomas F, Thornquist M, Ulrich CM, Warnick GS, Zanke BW, Peters U, Hsu L, White E
Source: Cancer Epidemiol Biomarkers Prev, 2014 Sep;23(9), p. 1824-33.
EPub date: 2014 Jul 3.
PMID: 24994789
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2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.
Authors: Li J, Lindström LS, Foo JN, Rafiq S, Schmidt MK, Pharoah PD, Michailidou K, Dennis J, Bolla MK, Wang Q, Van 't Veer LJ, Cornelissen S, Rutgers E, Southey MC, Apicella C, Dite GS, Hopper JL, Fasching PA, Haeberle L, Ekici AB, Beckmann MW, Blomqvist C, Muranen TA, Aittomäki K, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Hartikainen JM, Kataja V, Chenevix-Trench G, kConFab Investigators, Phillips KA, McLachlan SA, Lambrechts D, Thienpont B, Smeets A, Wildiers H, Chang-Claude J, Flesch-Janys D, Seibold P, Rudolph A, Giles GG, Baglietto L, Severi G, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Kristensen V, Alnćs GI, Borresen-Dale AL, Nord S, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Devilee P, Tollenaar R, Seynaeve C, Hooning M, Kriege M, Hollestelle A, van den Ouweland A, Li Y, Hamann U, Torres D, Ulmer HU, Rüdiger T, Shen CY, Hsiung CN, Wu PE, Chen ST, Teo SH, Taib NA, Har Yip C, Fuang Ho G, Matsuo K, Ito H, Iwata H, Tajima K, Kang D, Choi JY, Park SK, Yoo KY, Maishman T, Tapper WJ, Dunning A, Shah M, Luben R, Brown J, Khor CC, Eccles DM, Nevanlinna H, Easton D, Humphreys K, Liu J, Hall P, Czene K
Source: Nat Commun, 2014 Jun 17;5, p. 4051.
EPub date: 2014 Jun 17.
PMID: 24937182
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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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Genetic predisposition to in situ and invasive lobular carcinoma of the breast.
Authors: Sawyer E, Roylance R, Petridis C, Brook MN, Nowinski S, Papouli E, Fletcher O, Pinder S, Hanby A, Kohut K, Gorman P, Caneppele M, Peto J, Dos Santos Silva I, Johnson N, Swann R, Dwek M, Perkins KA, Gillett C, Houlston R, Ross G, De Ieso P, Southey MC, Hopper JL, Provenzano E, Apicella C, Wesseling J, Cornelissen S, Keeman R, Fasching PA, Jud SM, Ekici AB, Beckmann MW, Kerin MJ, Marme F, Schneeweiss A, Sohn C, Burwinkel B, Guénel P, Truong T, Laurent-Puig P, Kerbrat P, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Milne RL, Perez JI, Menéndez P, Benitez J, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Lichtner P, Schmutzler RK, Lochmann M, Brauch H, Fischer HP, Ko YD, GENICA Network, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Chenevix-Trench G, Investigators K, Lambrechts D, Weltens C, Van Limbergen E, Hatse S, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Radice P, Peterlongo P, Bonanni B, Volorio S, Giles GG, Severi G, Baglietto L, McLean CA, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labrčche F, Dumont M, Kristensen V, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Mulligan AM, Devillee P, Tollenaar RA, Seynaeve CM, Kriege M, Figueroa J, Chanock SJ, Sherman ME, Hooning MJ, Hollestelle A, van den Ouweland AM, van Deurzen CH, Li J, Czene K, Humphreys K, Cox A, Cross SS, Reed MW, Shah M, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Couch FJ, Hallberg E, González-Neira A, Pita G, Alonso MR, Tessier DC, Vincent D, Bacot F, Bolla MK, Wang Q, Dennis J, Michailidou K, Dunning AM, Hall P, Easton D, Pharoah P, Schmidt MK, Tomlinson I, Garcia-Closas M
Source: PLoS Genet, 2014 Apr;10(4), p. e1004285.
EPub date: 2014 Apr 17.
PMID: 24743323
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Estimating the heritability of colorectal cancer.
Authors: Jiao S, Peters U, Berndt S, Brenner H, Butterbach K, Caan BJ, Carlson CS, Chan AT, Chang-Claude J, Chanock S, Curtis KR, Duggan D, Gong J, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Kolonel LN, Le Marchand L, Potter JD, Rudolph A, Schoen RE, Seminara D, Slattery ML, White E, Hsu L
Source: Hum Mol Genet, 2014 Jul 15;23(14), p. 3898-905.
EPub date: 2014 Feb 21.
PMID: 24562164
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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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Meta-analysis of loci associated with age at natural menopause in African-American women.
Authors: Chen CT, Liu CT, Chen GK, Andrews JS, Arnold AM, Dreyfus J, Franceschini N, Garcia ME, Kerr KF, Li G, Lohman KK, Musani SK, Nalls MA, Raffel LJ, Smith J, Ambrosone CB, Bandera EV, Bernstein L, Britton A, Brzyski RG, Cappola A, Carlson CS, Couper D, Deming SL, Goodarzi MO, Heiss G, John EM, Lu X, Le Marchand L, Marciante K, Mcknight B, Millikan R, Nock NL, Olshan AF, Press MF, Vaiyda D, Woods NF, Taylor HA, Zhao W, Zheng W, Evans MK, Harris TB, Henderson BE, Kardia SL, Kooperberg C, Liu Y, Mosley TH, Psaty B, Wellons M, Windham BG, Zonderman AB, Cupples LA, Demerath EW, Haiman C, Murabito JM, Rajkovic A
Source: Hum Mol Genet, 2014 Jun 15;23(12), p. 3327-42.
EPub date: 2014 Feb 2.
PMID: 24493794
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