Grant Number:	5R01CA081203-04 Interpret this number
Primary Investigator:	Goldgar, David
Organization:	International Agency For Res On Cancer
Project Title:	Risk Estimation and Modifier Genes in Inherited Cancer
Fiscal Year:	2003

DESCRIPTION (Adapted from investigator's abstract): During the past decade, progress has been made in localizing and identifying specific genes such as BRCA1 and p16 which when altered can confer a markedly increased susceptibility to relatively common cancers. Although variations at these genes apparently increase risk of cancer at a variety of anatomical sites, there is controversy about the magnitude of these risks. Risks derived from population-based studies have produced lower estimates of risk than those estimated from studies of single large families or series of multiple high-risk families. Whether these differences reflect inherent biases in the methods used for risk estimation or represent the effects of modifying loci segregating in high-risk families is not obvious. Statistical methods for estimation of gene effects are relatively underdeveloped. Additionally, there have been no studies that examine the feasibility of mapping hypothesized modifier loci in the context of a total genome search. This project seeks to examine the efficiency and bias associated with various sampling designs and statistical methods for estimation of cancer risks due to such genes. Monte-Carlo simulation and existing datasets encompassing the three approaches described above will be used for the evaluation of a variety of methods. Several designs for a) testing the effect on risk modification of specific candidate loci; b) detecting the presence of residual genetic effects; and c) examining the power of different sampling designs for genome-wide screens to localize modifier loci also will be examined.




Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group.
Authors: Brohet R.M. , Goldgar D.E. , Easton D.F. , Antoniou A.C. , Andrieu N. , Chang-Claude J. , Peock S. , Eeles R.A. , Cook M. , Chu C. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2007-09-01; 25(25), p. 3831-6.
EPub date: 2007-07-16.
PMID: 17635951
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study.
Authors: Chang-Claude J. , Andrieu N. , Rookus M. , Brohet R. , Antoniou A.C. , Peock S. , Davidson R. , Izatt L. , Cole T. , Noguès C. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2007 Apr; 16(4), p. 740-6.
PMID: 17416765
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Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS).
Authors: Andrieu N. , Goldgar D.E. , Easton D.F. , Rookus M. , Brohet R. , Antoniou A.C. , Peock S. , Evans G. , Eccles D. , Douglas F. , et al. .
Source: Journal of the National Cancer Institute, 2006-04-19; 98(8), p. 535-44.
PMID: 16622123
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Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.
Authors: Antoniou A.C. , Pharoah P.D. , Narod S. , Risch H.A. , Eyfjord J.E. , Hopper J.L. , Olsson H. , Johannsson O. , Borg A. , Pasini B. , et al. .
Source: Journal of medical genetics, 2005 Jul; 42(7), p. 602-3.
PMID: 15994883
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A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes.
Authors: Antoniou A.C. , Goldgar D.E. , Andrieu N. , Chang-Claude J. , Brohet R. , Rookus M.A. , Easton D.F. .
Source: Genetic epidemiology, 2005 Jul; 29(1), p. 1-11.
PMID: 15880399
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Increased power for case-control studies of single nucleotide polymorphisms through incorporation of family history and genetic constraints.
Authors: Thompson D. , Witte J.S. , Slattery M. , Goldgar D. .
Source: Genetic epidemiology, 2004 Nov; 27(3), p. 215-24.
PMID: 15389928
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Polygenic inheritance of breast cancer: Implications for design of association studies.
Authors: Antoniou A.C. , Easton D.F. .
Source: Genetic epidemiology, 2003 Nov; 25(3), p. 190-202.
PMID: 14557987
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A full-likelihood method for the evaluation of causality of sequence variants from family data.
Authors: Thompson D. , Easton D.F. , Goldgar D.E. .
Source: American journal of human genetics, 2003 Sep; 73(3), p. 652-5.
EPub date: 2003-07-29.
PMID: 12900794
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Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.
Authors: Antoniou A. , Pharoah P.D. , Narod S. , Risch H.A. , Eyfjord J.E. , Hopper J.L. , Loman N. , Olsson H. , Johannsson O. , Borg A. , et al. .
Source: American journal of human genetics, 2003 May; 72(5), p. 1117-30.
EPub date: 2003-04-03.
PMID: 12677558
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The effect of disease penetrance, family size, and age of onset on family history with application to setting eligibility criteria for genetic testing.
Authors: Sibert A. , Goldgar D.E. .
Source: Familial cancer, 2003; 2(1), p. 35-42.
PMID: 14574165
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Cancer Incidence in BRCA1 mutation carriers.
Authors: Thompson D. , Easton D.F. , Breast Cancer Linkage Consortium .
Source: Journal of the National Cancer Institute, 2002-09-18; 94(18), p. 1358-65.
PMID: 12237281
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A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes.
Authors: Antoniou A.C. , Pharoah P.D. , McMullan G. , Day N.E. , Stratton M.R. , Peto J. , Ponder B.J. , Easton D.F. .
Source: British journal of cancer, 2002-01-07; 86(1), p. 76-83.
PMID: 11857015
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