Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
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BiBTeXGenome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
DOI: 10.1093/hmg/ddp372
Projects: GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer
Publication type: Journal article
Journal: Human molecular genetics
Human Diseases: Hereditary breast ovarian cancer syndrome
Citation: Human Molecular Genetics 18(22):4442-4456
Date Published: 15th Nov 2009
Registered Mode: imported from a bibtex file
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The German Consortium for Hereditary Breast and Ovarian Cancer HBOC has been founded in 1996 by the German Cancer Aid and has been funded by the German Cancer Aid until recently. GC-HBOC currently comprises 17 university centers providing genetic counseling, histopathological and molecular tissue analysis, genetic testing, and specific structured surveillance programs for early cancer detection at each clinical unit, all based on defined standard operating procedures.
Programme: LIFE Management Cluster
Public web page: http://www.konsortium-familiaerer-brustkrebs.de/
Start date: 1st Jan 1996
Projects: LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0002-7247-282X
Projects: LHA - Leipzig Health Atlas, LIFE Adult, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, LIFE Heart, MMML - Molecular mechanisms in malignant lymphoma, GLA - German Lymphoma Alliance, MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, HaematoOpt - Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, e:Med, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, NLP4CR - Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, SepNet - German Competence Network Sepsis, LIFE Child, HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, GGN - German Glioma Network, CAPSys - Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, CapSys - Systems Medicine of Community Acquired Pneumonia, ProstataCA, HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, SMITH - Smart Medical Information Technology for Healthcare, Task Force COVID-19 Leipzig, NFDI4Health, POLAR - Polypharmacy, Drug Interactions, Risks, Management of health information systems, LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application, Project Test Demonstrator, Fundus photography as tool for analysis of eyes of subjects with diabetes, Clinical Trials Leipzig, NFDI4Health - TA3 Services, STOP-NUC, SCALE-TORT, EarlyAMDRate
Institutions: Institute for Medical Informatics, Statistics and Epidemiology (IMISE)
https://orcid.org/0000-0001-8344-0658
Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, LIFE HNC - Head and Neck Cancer Group, SepNet - German Competence Network Sepsis, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, LIFE Child, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, LIFE Adult
Web page: https://www.uniklinikum-leipzig.de/einrichtungen/life
Taxonomy URI: http://purl.obolibrary.org/obo/DOID_5683
Synonyms: BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC)
Definitions: Xref MGI., An autosomal dominant disease characterized by the higher than normal tendency associated with BRCA1 and BRCA2 to develop breast and ovarian cancers in genetically related families.
