期刊
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
卷 21, 期 4, 页码 645-657出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-11-0888
关键词
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资金
- NIH [CA128978]
- NCI [CA116201]
- U.S. Department of Defence [W81XWH-10-1-0341]
- Breast Cancer Research Foundation
- Komen Foundation for the Cure
- Cancer Research UK (CR-UK) [C12292/A11174, C1287/A10118]
- European Community [223175 (HEALTH-F2-2009-223175)]
- Canadian Institutes of Health Research
- Canadian Breast Cancer Research Alliance [019511]
- Research Council of Lithuania [LIG-19/2010]
- Cancer Association of South Africa (CANSA)
- National Cancer Institute, NIH [RFA-CA-06-503]
- Breast Cancer Family Registry (BCFR)
- Neye Foundation
- Fundacion Mutua Madrilena
- Asociacion Espanola Contra el Cancer
- Spanish Ministry of Science and Innovation [FIS PI08 1120]
- Basque Foundation for Health Innovation and Research (BIOEF) [BIO07/CA/006]
- Ministero della Salute
- Ministero dell'Universita' e Ricerca [RBLAO3-BETH]
- Fondazione Italiana per la Ricerca sul Cancro
- Associazione Italiana per la Ricerca sulCancro [4017]
- Fondazione IRCCS Istituto Nazionale Tumori
- DKFZ
- CR-UK [C1287/A10118, C1287/A11990]
- NIHR
- Royal Marsden NHS Foundation Trust
- German Cancer Aid [109076]
- Centre of Molecular Medicine Cologne (CMMC)
- Ligue National Contre le Cancer
- Association for International Cancer Research Grant [AICR-07-0454]
- Association Le cancer du sein, parlons-en!
- Familial Cancer Registry at Georgetown University (NIH/NCI) [P30-CA051008]
- Cancer Genetics Network [HHSN261200744000C]
- Swing Fore the Cure
- Clinical Genetics Branch, DCEG
- Community Oncology and Prevention Trials Program-COPTRG
- Helsinki University Central Hospital
- Academy of Finland [132473]
- Finnish Cancer Society
- Sigrid Juselius Foundation
- Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]
- ZonMW [91109024]
- Hungarian Research Grant [KTIA-OTKACK-80745]
- Spanish Health Research Fund
- Carlos III Health Institute
- Catalan Health Institute
- Autonomous Government of Catalonia
- Polish Foundation of Science
- Postgraduate School of Molecular Medicine, Warsaw Medical University
- Icelandic Association Walking for Breast Cancer Research
- Landspitali University Hospital
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR)
- Ministero della Salute [RFPS 2006-5-341353, ACC2/R6.9]
- National Breast Cancer Foundation
- National Health and Medical Research Council (NHMRC)
- Queensland Cancer Fund
- Cancer Councils of New South Wales, Victoria, Tasmania
- Cancer Foundation of Western Australia
- NHMRC [145684, 288704, 454508]
- FCCC
- University of Kansas Cancer Center
- Kansas Bioscience Authority Eminent Scholar Program
- Jewish General Hospital
- Starr Cancer Consortium
- Norman and Carol Stone Cancer Research Initiative
- Kate and Robert Niehaus Clinical Cancer Research Initiative
- Lymphoma Foundation
- Sabin Family Research Initiative
- U.S. National Cancer Institute
- Westat, Inc.
- Russian Federation for Basic Research [10-04-92601, 10-04-92110, 11-04-00227]
- Federal Agency for Science and Innovations [16.512.11.2237]
- Cancer Care Ontario
- U.S. National Cancer Institute, NIH under RFA [CA-06-503]
- Ohio State University Comprehensive Cancer Center
- Instituto Toscano Tumori grant
- CARIF
- University Malaya
- Helen Diller Family Comprehensive Cancer Center at UCSF
- Avon Foundation
- Center for Translational and Policy Research in Personalized Medicine (TRANSPERS)
- NIH/NCI [P01 CA130818-02A1]
- CRUK
- American Cancer Society [SIOP-06-258-06-COUN]
- [ISCIIIRETIC RD06/0020/1051]
- [PI10/01422]
- [PI10/31488]
- [2009SGR290]
- [U01CA69631]
- [5U01CA113916]
- [NO2-CP-11019-50]
- [N02-CP-65504]
- Cancer Research UK [15007, 11174, 10118, 11022] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
- The Francis Crick Institute
- Cancer Research UK [10124] Funding Source: researchfish
Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 x 10(-4)] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 x 10(-4)) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 x 10(-3)). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645-57. (C) 2012 AACR.
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