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Grant Details

Grant Number: 5R01CA080978-03 Interpret this number
Primary Investigator: Narod, Steven
Organization: University Of Toronto
Project Title: The Natural History of Hereditary Breast Cancer
Fiscal Year: 2002


Abstract

DESCRIPTION (Adapted from the Applicant's Abstract): Approximately 12 percent of Ashkenazi Jewish women with breast cancer are carriers of mutations in one of two cancer susceptibility genes, BRCA1 and BRCA2. Both of these genes are associated with a very high lifetime risk of breast cancer (estimated to be between 57 percent and 90 percent). It is important to know if the natural history of hereditary breast cancer is different from non-hereditary breast cancer. BRCAl-associated breast cancers are typically of high grade, are estrogen and progesterone receptor negative, and are p53-mutation positive. All of these are adverse prognostic features. The purpose of the present study is to estimate the ten-year survival rate for breast cancer patients with BRCA1 and BRCA2 mutations, and to compare this to women without mutations. To do this, we will identify and evaluate 2,818 cases of breast cancer diagnosed in Israel in 1987 and 1988. Approximately 1,900 of these cases occurred in Ashkenazi Jewish women. These women were reported to the Israel Cancer Registry from 21 source hospitals throughout the country. We will obtain breast cancer tissue blocks, or precut slides, from the affiliated pathology departments. DNA samples extracted from the tumour specimens will be typed for three founder Jewish mutations in BRCA1 and BRCA2. We will obtain clinical information about tumour size and nodal status at diagnosis. We will obtain demographic information about the year and place of birth of the patient and her religion and ethnic group. We will obtain current vital status, and if dead, year and cause of death. We will estimate the ten year survival rate for hereditary breast cancer and compare this with that for non-hereditary cases. We will compare survival rates for BRCA1 and BRCA2 carriers separately. We will also study the influence of BRCA1/BRCA2 mutations in the subgroup of lymph-node negative breast cancers.



Publications

Evidence of a genetic link between endometriosis and ovarian cancer.
Authors: Lee A.W. , Templeman C. , Stram D.A. , Beesley J. , Tyrer J. , Berchuck A. , Pharoah P.P. , Chenevix-Trench G. , Pearce C.L. , Ovarian Cancer Association Consortium .
Source: Fertility and sterility, 2016 Jan; 105(1), p. 35-43.e1-10.
EPub date: 2015-10-23.
PMID: 26477498
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Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.
Authors: Lu Y. , Cuellar-Partida G. , Painter J.N. , Nyholt D.R. , Australian Ovarian Cancer Study , International Endogene Consortium (IEC) , Morris A.P. , Fasching P.A. , Hein A. , Burghaus S. , et al. .
Source: Human molecular genetics, 2015-10-15; 24(20), p. 5955-64.
EPub date: 2015-07-30.
PMID: 26231222
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Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study.
Authors: Lee A.W. , Tyrer J.P. , Doherty J.A. , Stram D.A. , Kupryjanczyk J. , Dansonka-Mieszkowska A. , Plisiecka-Halasa J. , Spiewankiewicz B. , Myers E.J. , Australian Cancer Study (Ovarian Cancer) , et al. .
Source: Gynecologic oncology, 2015 Mar; 136(3), p. 542-8.
EPub date: 2014-12-17.
PMID: 25528498
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Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.
Authors: Chornokur G. , Lin H.Y. , Tyrer J.P. , Lawrenson K. , Dennis J. , Amankwah E.K. , Qu X. , Tsai Y.Y. , Jim H.S. , Chen Z. , et al. .
Source: PloS one, 2015; 10(6), p. e0128106.
EPub date: 2015-06-19.
PMID: 26091520
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Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.
Authors: Kelemen L.E. , Terry K.L. , Goodman M.T. , Webb P.M. , Bandera E.V. , McGuire V. , Rossing M.A. , Wang Q. , Dicks E. , Tyrer J.P. , et al. .
Source: Molecular nutrition & food research, 2014 Oct; 58(10), p. 2023-35.
EPub date: 2014-07-28.
PMID: 25066213
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Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer.
Authors: Block M.S. , Charbonneau B. , Vierkant R.A. , Fogarty Z. , Bamlet W.R. , Pharoah P.D. , Georgia Chenevix-Trench , for AOCS , /ACS Group , Rossing M.A. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Jul; 23(7), p. 1421-7.
EPub date: 2014-04-16.
PMID: 24740199
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Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA.
Authors: Earp M.A. , Kelemen L.E. , Magliocco A.M. , Swenerton K.D. , Chenevix-Trench G. , Australian Cancer Study , Australian Ovarian Cancer Study Group , Lu Y. , Hein A. , Ekici A.B. , et al. .
Source: Human genetics, 2014 May; 133(5), p. 481-97.
EPub date: 2013-11-05.
PMID: 24190013
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Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome.
Authors: Charbonneau B. , Moysich K.B. , Kalli K.R. , Oberg A.L. , Vierkant R.A. , Fogarty Z.C. , Block M.S. , Maurer M.J. , Goergen K.M. , Fridley B.L. , et al. .
Source: Cancer immunology research, 2014 Apr; 2(4), p. 332-40.
EPub date: 2014-01-27.
PMID: 24764580
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Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.
Authors: Charbonneau B. , Block M.S. , Bamlet W.R. , Vierkant R.A. , Kalli K.R. , Fogarty Z. , Rider D.N. , Sellers T.A. , Tworoger S.S. , Poole E. , et al. .
Source: Cancer research, 2014-02-01; 74(3), p. 852-61.
EPub date: 2013-11-22.
PMID: 24272484
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Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome.
Authors: White K.L. , Vierkant R.A. , Fogarty Z.C. , Charbonneau B. , Block M.S. , Pharoah P.D. , Chenevix-Trench G. , for AOCS/ACS group; , Rossing M.A. , Cramer D.W. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013 May; 22(5), p. 987-92.
EPub date: 2013-03-19.
PMID: 23513043
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Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.
Authors: Faber M.T. , Kjær S.K. , Dehlendorff C. , Chang-Claude J. , Andersen K.K. , Høgdall E. , Webb P.M. , Jordan S.J. , Australian Cancer Study (Ovarian Cancer) , Australian Ovarian Cancer Study Group , et al. .
Source: Cancer causes & control : CCC, 2013 May; 24(5), p. 989-1004.
EPub date: 2013-03-02.
PMID: 23456270
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Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.
Authors: Shen H. , Fridley B.L. , Song H. , Lawrenson K. , Cunningham J.M. , Ramus S.J. , Cicek M.S. , Tyrer J. , Stram D. , Larson M.C. , et al. .
Source: Nature communications, 2013; 4, p. 1628.
PMID: 23535649
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Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.
Authors: Permuth-Wey J. , Lawrenson K. , Shen H.C. , Velkova A. , Tyrer J.P. , Chen Z. , Lin H.Y. , Chen Y.A. , Tsai Y.Y. , Qu X. , et al. .
Source: Nature communications, 2013; 4, p. 1627.
PMID: 23535648
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Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.
Authors: Pal T. , Akbari M.R. , Sun P. , Lee J.H. , Fulp J. , Thompson Z. , Coppola D. , Nicosia S. , Sellers T.A. , McLaughlin J. , et al. .
Source: British journal of cancer, 2012-11-06; 107(10), p. 1783-90.
EPub date: 2012-10-09.
PMID: 23047549
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ABO blood group and risk of epithelial ovarian cancer within the Ovarian Cancer Association Consortium.
Authors: Poole E.M. , Gates M.A. , High B.A. , Chanock S.J. , Cramer D.W. , Cunningham J.M. , Fridley B.L. , Gayther S.A. , Goode E.L. , Iversen E.S. , et al. .
Source: Cancer causes & control : CCC, 2012 Nov; 23(11), p. 1805-10.
EPub date: 2012-09-08.
PMID: 22961099
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The risk of developing uterine sarcoma after tamoxifen use.
Authors: Lavie O. , Barnett-Griness O. , Narod S.A. , Rennert G. .
Source: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2008 Mar-Apr; 18(2), p. 352-6.
PMID: 18334013
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