Grant Number:	1R01CA105090-01A1 Interpret this number
Primary Investigator:	Parmigiani, Giovanni
Organization:	Johns Hopkins University
Project Title:	Statistical Methods for Cancer Genes
Fiscal Year:	2004

DESCRIPTION (provided by applicant): Identifying individuals at high risk of cancer because of inherited genetic susceptibility is complex and increasingly important. Probabilistic prediction algorithms that exploit domain knowledge of Mendelian inheritance and other biological characteristics of susceptibility genes successfully contribute to improved screening, prevention, and genetic testing, and to the design and analysis of cancer studies. The investigators have developed, validated, applied and disseminated the widely used Mendelian model BRCAPRO. Based on their experience they have identified the need for a new generation of Mendelian prediction models in cancer genetics. The first aim will develop statistical approaches that generalize Mendelian models currently used in clinical genetic counseling practice. Innovation will focus on five areas: A) accounting for errors in reported pedigrees; B) accounting for dependencies in time-to-event distributions for multiple cancer sites; C) accounting for familial correlations arising from shared environmental factors or other sources; D) accounting for multiallelic syndromes; and E) incorporating information on covariates and on biomarkers related to the genes' activity. The second aim will introduce a novel class of multi-syndrome models to simultaneously identify cancer syndromes and predict mutation carrier status. These will enable clinicians and researchers to address the emerging challenges posed by the overlap in phenotype for cancer susceptibility genes, and by the high frequency of sporadic families with multiple sites. The third aim will develop flexible user-friendly software for the application of the methods in both research and clinical settings. The aims of this proposal will overcome pressing practical limitations of tools currently used in clinical genetic counseling, and thus contribute to improved screening, prevention and decision making about genetic testing.




Estimating Cdkn2a Carrier Probability And Personalizing Cancer Risk Assessments In Hereditary Melanoma Using Melapro
Authors: Wang,W. , Niendorf,K.B. , Patel,D. , Blackford,A. , Marroni,F. , Sober,A.J. , Parmigiani,G. , Tsao,H. .
Source: Cancer Research, 2010-01-15 00:00:00.0; 70(2), p. 552-9.
PMID: 20068151
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Tailoring Brcapro To Asian-americans
Authors: Chen,S. , Blackford,A.L. , Parmigiani,G. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2009-02-01 00:00:00.0; 27(4), p. 642-3; author reply 643-4.
PMID: 19075251
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The Ordering Of Expression Among A Few Genes Can Provide Simple Cancer Biomarkers And Signal Brca1 Mutations
Authors: Lin,X. , Afsari,B. , Marchionni,L. , Cope,L. , Parmigiani,G. , Naiman,D. , Geman,D. .
Source: Bmc Bioinformatics, 2009; 10, p. 256.
PMID: 19695104
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Multiple Diseases In Carrier Probability Estimation: Accounting For Surviving All Cancers Other Than Breast And Ovary In Brcapro
Authors: Katki,H.A. , Blackford,A. , Chen,S. , Parmigiani,G. .
Source: Statistics In Medicine, 2008-09-30 00:00:00.0; 27(22), p. 4532-48.
PMID: 18407567
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Estimating Genome-wide Copy Number Using Allele-specific Mixture Models
Authors: Wang,W. , Carvalho,B. , Miller,N.D. , Pevsner,J. , Chakravarti,A. , Irizarry,R.A. .
Source: Journal Of Computational Biology : A Journal Of Computational Molecular Cell Biology, 2008 Sep; 15(7), p. 857-66.
PMID: 18707534
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Comparative lesion sequencing provides insights into tumor evolution.
Authors: Jones S. , Chen W.D. , Parmigiani G. , Diehl F. , Beerenwinkel N. , Antal T. , Traulsen A. , Nowak M.A. , Siegel C. , Velculescu V.E. , et al. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008-03-18 00:00:00.0; 105(11), p. 4283-8.
EPub date: 2008-03-18 00:00:00.0.
PMID: 18337506
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Breast cancer risk among male BRCA1 and BRCA2 mutation carriers.
Authors: Tai Y.C. , Domchek S. , Parmigiani G. , Chen S. .
Source: Journal Of The National Cancer Institute, 2007-12-05 00:00:00.0; 99(23), p. 1811-4.
EPub date: 2007-12-05 00:00:00.0.
PMID: 18042939
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Validity of models for predicting BRCA1 and BRCA2 mutations.
Authors: Parmigiani G. , Chen S. , Iversen E.S. , Friebel T.M. , Finkelstein D.M. , Anton-Culver H. , Ziogas A. , Weber B.L. , Eisen A. , Malone K.E. , et al. .
Source: Annals Of Internal Medicine, 2007-10-02 00:00:00.0; 147(7), p. 441-50.
PMID: 17909205
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A Multidimensional Analysis Of Genes Mutated In Breast And Colorectal Cancers
Authors: Lin,J. , Gan,C.M. , Zhang,X. , Jones,S. , Sjöblom,T. , Wood,L.D. , Parsons,D.W. , Papadopoulos,N. , Kinzler,K.W. , Vogelstein,B. , et al. .
Source: Genome Research, 2007 Sep; 17(9), p. 1304-18.
PMID: 17693572
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Meta-analysis Of Brca1 And Brca2 Penetrance
Authors: Chen,S. , Parmigiani,G. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2007-04-10 00:00:00.0; 25(11), p. 1329-33.
PMID: 17416853
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Pancpro: Risk Assessment For Individuals With A Family History Of Pancreatic Cancer
Authors: Wang,W. , Chen,S. , Brune,K.A. , Hruban,R.H. , Parmigiani,G. , Klein,A.P. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2007-04-10 00:00:00.0; 25(11), p. 1417-22.
PMID: 17416862
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Incorporating Medical Interventions Into Carrier Probability Estimation For Genetic Counseling
Authors: Katki,H.A. .
Source: Bmc Medical Genetics, 2007; 8, p. 13.
PMID: 17378937
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A Recessive Mendelian Model To Predict Carrier Probabilities Of Dfnb1 For Nonsyndromic Deafness
Authors: González,J.R. , Wang,W. , Ballana,E. , Estivill,X. .
Source: Human Mutation, 2006 Nov; 27(11), p. 1135-42.
PMID: 16941638
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Prediction of germline mutations and cancer risk in the Lynch syndrome.
Authors: Chen S. , Wang W. , Lee S. , Nafa K. , Lee J. , Romans K. , Watson P. , Gruber S.B. , Euhus D. , Kinzler K.W. , et al. .
Source: Jama, 2006-09-27 00:00:00.0; 296(12), p. 1479-87.
PMID: 17003396
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Effect Of Misreported Family History On Mendelian Mutation Prediction Models
Authors: Katki,H.A. .
Source: Biometrics, 2006 Jun; 62(2), p. 478-87.
PMID: 16918912
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Characterization of BRCA1 and BRCA2 mutations in a large United States sample.
Authors: Chen S. , Iversen E.S. , Friebel T. , Finkelstein D. , Weber B.L. , Eisen A. , Peterson L.E. , Schildkraut J.M. , Isaacs C. , Peshkin B.N. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2006-02-20 00:00:00.0; 24(6), p. 863-71.
PMID: 16484695
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A Markov Chain Monte Carlo Technique For Identification Of Combinations Of Allelic Variants Underlying Complex Diseases In Humans
Authors: Favorov,A.V. , Andreewski,T.V. , Sudomoina,M.A. , Favorova,O.O. , Parmigiani,G. , Ochs,M.F. .
Source: Genetics, 2005 Dec; 171(4), p. 2113-21.
PMID: 16118183
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Accuracy Of Msi Testing In Predicting Germline Mutations Of Msh2 And Mlh1: A Case Study In Bayesian Meta-analysis Of Diagnostic Tests Without A Gold Standard
Authors: Chen,S. , Watson,P. , Parmigiani,G. .
Source: Biostatistics (oxford, England), 2005 Jul; 6(3), p. 450-64.
PMID: 15831578
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Population-Calibrated Gene Characterization: Estimating Age at Onset Distributions Associated With Cancer Genes.
Authors: Iversen E.S. , Chen S. .
Source: Journal Of The American Statistical Association, 2005; 100, p. 399-409.
PMID: 18418465
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Classification of Missense Mutations of Disease Genes.
Authors: Zhou X. , Iversen E.S. , Parmigiani G. .
Source: Journal Of The American Statistical Association, 2005; 100, p. 51-60.
PMID: 18418466
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Bayesmendel: An R Environment For Mendelian Risk Prediction
Authors: Chen,S. , Wang,W. , Broman,K.W. , Katki,H.A. , Parmigiani,G. .
Source: Statistical Applications In Genetics And Molecular Biology, 2004; 3, p. Article21.
PMID: 16646800
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