Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Several common germline variants identified through genome-wide association studies of breast cancer risk in the general population have recently been shown to be associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. When combined, these variants can identify marked differences in the absolute risk of developing breast cancer for mutation carriers, suggesting that additional modifier loci may further enhance individual risk assessment for BRCA1 and BRCA2 mutation carriers. Recently, a common variant on 6p22 (rs9393597) was found to be associated with increased breast cancer risk for BRCA2 mutation carriers [hazard ratio (HR) = 1.55, 95 % confidence interval (CI) 1.25-1.92, p = 6.0 × 10(-5)]. This observation was based on data from GWAS studies in which, despite statistical correction for multiple comparisons, the possibility of false discovery remains a concern. Here, we report on an analysis of this variant in an additional 6,165 BRCA1 and 3,900 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). In this replication analysis, rs9393597 was not associated with breast cancer risk for BRCA2 mutation carriers (HR = 1.09, 95 % CI 0.96-1.24, p = 0.18). No association with ovarian cancer risk for BRCA1 or BRCA2 mutation carriers or with breast cancer risk for BRCA1 mutation carriers was observed. This follow-up study suggests that, contrary to our initial report, this variant is not associated with breast cancer risk among individuals with germline BRCA2 mutations.Cancer Research UK C12292/A11174 C1287/A10118 National Institutes of Health CA128978 Komen Foundation for the Cure Breast Cancer Research Foundation (BCRF) NIH CA128978 CA74415 R01-CA083855 R01-CA9677 CA122340 City of Hope Clinical Cancer Genetics Community Network Hereditary Cancer Research Registry from the National Cancer Institute RC4CA153828 Office of the Director, National Institutes of Health Susan G. Komen for the Cure Mayo Clinic Breast Cancer SPORE P50-CA116201 Fondazione Italiana per la Ricerca sul Cancro Associazione Italiana per la Ricerca sul Cancro 8713 Italian Ministry of Health Italian Ministry of Education, University and Research Fondazione IRCCS Istituto Nazionale Tumori Mayo Rochester Early Career Development Award for Non-Clinician Scientists Grant Agency of the Czech Republic GP301/08/P103 Fund for Scientific Research Flanders (FWO) 1.5.150.07 Ghent University 12051203 Fund for Scientific Research of Flanders (FWO-Vlaanderen) Vlaamse Liga tegen Kanker through a grant of the Foundation Emmanuel van der Schueren Ministry of Health CR-MZ0 MOU 2005 Intramural Research Program of the US National Cancer Institute Israel Cancer Association (ICA) Cancer Genetics Network Marjorie Cohen Foundation Fundacion Mutua Madrilena Asociacion Espanola Contra el Cancer Spanish Ministry of Science and Innovation FIS PI08 1120 FIS 09/00859 RD06/0020/0021 Basque Foundation for Health Innovation and Research (BIOEF) BIO07/CA/006 DKFZ Cancer Research-UK C1287/A10118 C1287/A8874 C8197/A10123 Dutch Cancer Society NKI19981854 NKI2004-3088 NKI2007-3756 NWO 91109024 Pink Ribbon Grant 110005 BBMRI Grant CP46/NWO National Cancer Institute, National Institutes of Health RFACA-06-503 Ligue National Contre le Cancer Association for International Cancer Research AICR-07-0454 Association "Le cancer du sein, parlons-en!" Award National Cancer Institute CA 27469 GOG Tissue Bank CA 27469 Gynecologic Oncology Group Statistical and Data Center CA 37517 CA 101165 OSU Comprehensive Cancer Center Ministero dell'Universita e della Ricerca Ministero della Salute Alleanza Contro il Cancro Russian Foundation for Basic Research 08-04-00369-a 09-04-90402 10-04-92110-a Commission of the European Communities PITN-GA-2009-238132 Royal Society International Joint Grant JP090615 Latvian Science Council Grant 10.0010.08 American Cancer Society Early Detection Professorship Entertainment Industry Foundation German Cancer Aid 107054 Helsinki University Central Hospital Research Fund, Academy of Finland 132473 Finnish Cancer Society Sigrid Juselius Foundation Canadian Institutes of Health Research Canadian Breast Cancer Research Alliance 019511 NHMRC 145684 288704 454508 National Breast Cancer Foundation Cancer Australia 628333 Queensland Cancer Fund Cancer Council of New South Wales Cancer Council of Victoria Cancer Councils of Tasmania Cancer Councils of South Australia Cancer Foundation of Western Australia Landspitali University Hospital Research Fund Icelandic association Sandra Taub Research Fund of the BCRF NO2-CP-11019-50 N02-CP-65504 PBZ_ KBN_122/P05/200