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Grant Details

Grant Number: 5U19CA148537-04 Interpret this number
Primary Investigator: Henderson, Brian
Organization: University Of Southern California
Project Title: Elucidating Loci Involved in Prostate Cancer Suceptibility
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): We propose to establish a multidisciplinary team of epidemiologists, statisticians, basic scientists and clinician scientists to promote and pursue thorough identification and characterization of genomic loci associated with prostate cancer. ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) is a translational grant comprised of three highly integrated projects. Project 1 aims to take advantage of existing and shortly to be completed GWAS of prostate cancer in European, African American, Latino and Japanese populations to discover novel risk loci, and to rigorously replicate these associations in large existing consortia of prostate cases and controls (PRACTICAL, BPC3, and MADCaP). A major focus of this expanded effort is to identify loci that may selectively be associated with advanced disease and variants that contribute to ethnic difference in disease risk. Selective fine mapping of risk loci will also be performed to comprehensively characterize the relevant allelic locus, utilizing all available data on common variants from Hapmap, selective sequencing efforts, and from the 1000 Genome Project. Project 2 is focused on understanding the gene(s) that the non-protein coding risk variants are acting through. Two hypotheses will be systematically explored using a wide variety of established and emerging techniques: the risk loci harbor as yet undetected transcripts (either coding or non-coding) and the risk loci are regulatory elements. Finally, in Project 3 we propose to investigate the potential of this new knowledge on the genetic basis of prostate cancer susceptibility to enhance risk assessment, through gene-gene and gene-environment interactions, and importantly, to provide the potential for novel clinical practices through impacts on cancer diagnosis and treatment, or newer cancer prevention strategies. The overarching goal is to discover the pathways that drive prostate cancer pathogenesis and to assess their role in clinical decision making.

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Publications

A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
Authors: Al Olama AA, Kote-Jarai Z, Berndt SI, Conti DV, Schumacher F, Han Y, Benlloch S, Hazelett DJ, Wang Z, Saunders E, Leongamornlert D, Lindstrom S, Jugurnauth-Little S, Dadaev T, Tymrakiewicz M, Stram DO, Rand K, Wan P, Stram A, Sheng X, Pooler LC, Park K, Xia L, Tyrer J, Kolonel LN, Le Marchand L, Hoover RN, Machiela MJ, Yeager M, Burdette L, Chung CC, Hutchinson A, Yu K, Goh C, Ahmed M, Govindasami K, Guy M, Tammela TL, Auvinen A, Wahlfors T, Schleutker J, Visakorpi T, Leinonen KA, Xu J, Aly M, Donovan J, Travis RC, Key TJ, Siddiq A, Canzian F, Khaw KT, Takahashi A, Kubo M, Pharoah P, Pashayan N, Weischer M, Nordestgaard BG, Nielsen SF, Klarskov P, Rřder MA, Iversen P, Thibodeau SN, McDonnell SK, Schaid DJ, Stanford JL, Kolb S, Holt S, Knudsen B, Coll AH, Gapstur SM, Diver WR, Stevens VL, Maier C, Luedeke M, Herkommer K, Rinckleb AE, Strom SS, Pettaway C, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Chokkalingam AP, Cannon-Albright L, Cybulski C, Woko?orczyk D, Klu?niak W, Park J, Sellers T, Lin HY, Isaacs WB, Partin AW, Brenner H, Dieffenbach AK, Stegmaier C, Chen C, Giovannucci EL, Ma J, Stampfer M, Penney KL, Mucci L, John EM, Ingles SA, Kittles RA, Murphy AB, Pandha H, Michael A, Kierzek AM, Blot W, Signorello LB, Zheng W, Albanes D, Virtamo J, Weinstein S, Nemesure B, Carpten J, Leske C, Wu SY, Hennis A, Kibel AS, Rybicki BA, Neslund-Dudas C, Hsing AW, Chu L, Goodman PJ, Klein EA, Zheng SL, Batra J, Clements J, Spurdle A, Teixeira MR, Paulo P, Maia S, Slavov C, Kaneva R, Mitev V, Witte JS, Casey G, Gillanders EM, Seminara D, Riboli E, Hamdy FC, Coetzee GA, Li Q, Freedman ML, Hunter DJ, Muir K, Gronberg H, Neal DE, Southey M, Giles GG, Severi G, Breast and Prostate Cancer Cohort Consortium (BPC3), PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, COGS (Collaborative Oncological Gene-environment Study) Consortium, GAME-ON/ELLIPSE Consortium, Cook MB, Nakagawa H, Wiklund F, Kraft P, Chanock SJ, Henderson BE, Easton DF, Eeles RA, Haiman CA
Source: Nat Genet, 2014 Oct;46(10), p. 1103-9.
EPub date: 2014 Sep 14.
PMID: 25217961
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Translating genetic risk factors for prostate cancer to the clinic: 2013 and beyond.
Authors: Mikropoulos C, Goh C, Leongamornlert D, Kote-Jarai Z, Eeles R
Source: Future Oncol, 2014;10(9), p. 1679-94.
PMID: 25145435
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Generalizability of established prostate cancer risk variants in men of African ancestry.
Authors: Han Y, Signorello LB, Strom SS, Kittles RA, Rybicki BA, Stanford JL, Goodman PJ, Berndt SI, Carpten J, Casey G, Chu L, Conti DV, Rand KA, Diver WR, Hennis AJ, John EM, Kibel AS, Klein EA, Kolb S, Marchand LL, Leske MC, Murphy AB, Neslund-Dudas C, Park JY, Pettaway C, Rebbeck TR, Gapstur SM, Zheng SL, Wu SY, Witte JS, Xu J, Isaacs W, Ingles SA, Hsing A, The PRACTICAL Consortium, The ELLIPSE GAME-ON Consortium, Easton DF, Eeles RA, Schumacher FR, Chanock S, Nemesure B, Blot WJ, Stram DO, Henderson BE, Haiman CA
Source: Int J Cancer, 2014 Jul 8;null, p. null.
EPub date: 2014 Jul 8.
PMID: 25044450
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The role of local ancestry adjustment in association studies using admixed populations.
Authors: Zhang J, Stram DO
Source: Genet Epidemiol, 2014 Sep;38(6), p. 502-15.
EPub date: 2014 Jul 15.
PMID: 25043967
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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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Expression QTL-based analyses reveal candidate causal genes and loci across five tumor types.
Authors: Li Q, Stram A, Chen C, Kar S, Gayther S, Pharoah P, Haiman C, Stranger B, Kraft P, Freedman ML
Source: Hum Mol Genet, 2014 Oct 1;23(19), p. 5294-302.
EPub date: 2014 Jun 6.
PMID: 24907074
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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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Shared common variants in prostate cancer and blood lipids.
Authors: Andreassen OA, Zuber V, Thompson WK, Schork AJ, Bettella F, PRACTICAL Consortium, CRUK GWAS, Djurovic S, Desikan RS, Mills IG, Dale AM
Source: Int J Epidemiol, 2014 Aug;43(4), p. 1205-14.
EPub date: 2014 Apr 30.
PMID: 24786909
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Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome.
Authors: Charbonneau B, Moysich KB, Kalli KR, Oberg AL, Vierkant RA, Fogarty ZC, Block MS, Maurer MJ, Goergen KM, Fridley BL, Cunningham JM, Rider DN, Preston C, Hartmann LC, Lawrenson K, Wang C, Tyrer J, Song H, deFazio A, Johnatty SE, Doherty JA, Phelan CM, Sellers TA, Ramirez SM, Vitonis AF, Terry KL, Van Den Berg D, Pike MC, Wu AH, Berchuck A, Gentry-Maharaj A, Ramus SJ, Diergaarde B, Shen H, Jensen A, Menkiszak J, Cybulski C, Lubi?ski J, Ziogas A, Rothstein JH, McGuire V, Sieh W, Lester J, Walsh C, Vergote I, Lambrechts S, Despierre E, Garcia-Closas M, Yang H, Brinton LA, Spiewankiewicz B, Rzepecka IK, Dansonka-Mieszkowska A, Seibold P, Rudolph A, Paddock LE, Orlow I, Lundvall L, Olson SH, Hogdall CK, Schwaab I, du Bois A, Harter P, Flanagan JM, Brown R, Paul J, Ekici AB, Beckmann MW, Hein A, Eccles D, Lurie G, Hays LE, Bean YT, Pejovic T, Goodman MT, Campbell I, Fasching PA, Konecny G, Kaye SB, Heitz F, Hogdall E, Bandera EV, Chang-Claude J, Kupryjanczyk J, Wentzensen N, Lambrechts D, Karlan BY, Whittemore AS, Culver HA, Gronwald J, Levine DA, Kjaer SK, Menon U, Schildkraut JM, Pearce CL, Cramer DW, Rossing MA, Chenevix-Trench G, AOCS group, ACS, Pharoah PD, Gayther SA, Ness RB, Odunsi K, Sucheston LE, Knutson KL, Goode EL
Source: Cancer Immunol Res, 2014 Apr;2(4), p. 332-40.
EPub date: 2014 Jan 27.
PMID: 24764580
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Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer.
Authors: Block MS, Charbonneau B, Vierkant RA, Fogarty Z, Bamlet WR, Pharoah PD, Georgia Chenevix-Trench, for AOCS, /ACS Group, Rossing MA, Cramer D, Pearce CL, Schildkraut J, Menon U, Kjaer SK, Levine DA, Gronwald J, Culver HA, Whittemore AS, Karlan BY, Lambrechts D, Wentzensen N, Kupryjanczyk J, Chang-Claude J, Bandera EV, Hogdall E, Heitz F, Kaye SB, Fasching PA, Campbell I, Goodman MT, Pejovic T, Bean YT, Hays LE, Lurie G, Eccles D, Hein A, Beckmann MW, Ekici AB, Paul J, Brown R, Flanagan JM, Harter P, du Bois A, Schwaab I, Hogdall CK, Lundvall L, Olson SH, Orlow I, Paddock LE, Rudolph A, Eilber U, Dansonka-Mieszkowska A, Rzepecka IK, Ziolkowska-Seta I, Brinton LA, Yang H, Garcia-Closas M, Despierre E, Lambrechts S, Vergote I, Walsh CS, Lester J, Sieh W, McGuire V, Rothstein JH, Ziogas A, Lubi?ski J, Cybulski C, Menkiszak J, Jensen A, Gayther SA, Ramus SJ, Gentry-Maharaj A, Berchuck A, Wu AH, Pike MC, Van Den Berg D, Terry KL, Vitonis AF, Ramirez SM, Rider DN, Knutson KL, Sellers TA, Phelan CM, Doherty JA, Johnatty SE, deFazio A, Song H, Tyrer J, Kalli KR, Fridley BL, Cunningham JM, Goode EL
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jul;23(7), p. 1421-7.
EPub date: 2014 Apr 16.
PMID: 24740199
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DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.
Authors: Osorio A, Milne RL, Kuchenbaecker K, Vaclová T, Pita G, Alonso R, Peterlongo P, Blanco I, de la Hoya M, Duran M, Díez O, Ramón Y Cajal T, Konstantopoulou I, Martínez-Bouzas C, Andrés Conejero R, Soucy P, McGuffog L, Barrowdale D, Lee A, Swe-Brca, Arver B, Rantala J, Loman N, Ehrencrona H, Olopade OI, Beattie MS, Domchek SM, Nathanson K, Rebbeck TR, Arun BK, Karlan BY, Walsh C, Lester J, John EM, Whittemore AS, Daly MB, Southey M, Hopper J, Terry MB, Buys SS, Janavicius R, Dorfling CM, van Rensburg EJ, Steele L, Neuhausen SL, Ding YC, Hansen TV, Jřnson L, Ejlertsen B, Gerdes AM, Infante M, Herráez B, Moreno LT, Weitzel JN, Herzog J, Weeman K, Manoukian S, Peissel B, Zaffaroni D, Scuvera G, Bonanni B, Mariette F, Volorio S, Viel A, Varesco L, Papi L, Ottini L, Tibiletti MG, Radice P, Yannoukakos D, Garber J, Ellis S, Frost D, Platte R, Fineberg E, Evans G, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Eccles D, Cook J, Hodgson S, Brewer C, Tischkowitz M, Douglas F, Porteous M, Side L, Walker L, Morrison P, Donaldson A, Kennedy J, Foo C, Godwin AK, Schmutzler RK, Wappenschmidt B, Rhiem K, Engel C, Meindl A, Ditsch N, Arnold N, Plendl HJ, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Gehrig A, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Damiola F, Poppe B, Claes K, Piedmonte M, Tucker K, Backes F, Rodríguez G, Brewster W, Wakeley K, Rutherford T, Caldés T, Nevanlinna H, Aittomäki K, Rookus MA, van Os TA, van der Kolk L, de Lange JL, Meijers-Heijboer HE, van der Hout AH, van Asperen CJ, Gómez Garcia EB, Hoogerbrugge N, Collée JM, van Deurzen CH, van der Luijt RB, Devilee P, Hebon, Olah E, Lázaro C, Teulé A, Menéndez M, Jakubowska A, Cybulski C, Gronwald J, Lubinski J, Durda K, Jaworska-Bieniek K, Johannsson OT, Maugard C, Montagna M, Tognazzo S, Teixeira MR, Healey S, Investigators K, Olswold C, Guidugli L, Lindor N, Slager S, Szabo CI, Vijai J, Robson M, Kauff N, Zhang L, Rau-Murthy R, Fink-Retter A, Singer CF, Rappaport C, Geschwantler Kaulich D, Pfeiler G, Tea MK, Berger A, Phelan CM, Greene MH, Mai PL, Lejbkowicz F, Andrulis I, Mulligan AM, Glendon G, Toland AE, Bojesen A, Pedersen IS, Sunde L, Thomassen M, Kruse TA, Jensen UB, Friedman E, Laitman Y, Shimon SP, Simard J, Easton DF, Offit K, Couch FJ, Chenevix-Trench G, Antoniou AC, Benitez J
Source: PLoS Genet, 2014 Apr;10(4), p. e1004256.
EPub date: 2014 Apr 3.
PMID: 24698998
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Lymphocyte telomere length is long in BRCA1 and BRCA2 mutation carriers regardless of cancer-affected status.
Authors: Pooley KA, McGuffog L, Barrowdale D, Frost D, Ellis SD, Fineberg E, Platte R, Izatt L, Adlard J, Bardwell J, Brewer C, Cole T, Cook J, Davidson R, Donaldson A, Dorkins H, Douglas F, Eason J, Houghton C, Kennedy MJ, McCann E, Miedzybrodzka Z, Murray A, Porteous ME, Rogers MT, Side LE, Tischkowitz M, Walker L, Hodgson S, Eccles DM, Morrison PJ, Evans DG, Eeles RA, Antoniou AC, Easton DF, Dunning AM, EMBRACE;
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jun;23(6), p. 1018-24.
EPub date: 2014 Mar 18.
PMID: 24642354
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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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