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Breast Cancer Risk Genes — Association Analysis in More than 113,000 Women

2021· article· en· 1 154 citations· W3100475287 sur OpenAlex· 10.1056/nejmoa1913948

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Résumé

BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: , missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).

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La notice

Revue
New England Journal of Medicine
Thématique
BRCA gene mutations in cancer
Domaine
Biochemistry, Genetics and Molecular Biology
Établissements canadiens
Organismes subventionnaires
Division of Cancer Epidemiology and Genetics, National Cancer InstituteInstitute of GeneticsNational Cancer InstituteErasmus Universitair Medisch Centrum RotterdamCancer Council VictoriaManchester Biomedical Research CentreDirectorate for Biological SciencesNational Institutes of HealthÖrebro UniversitetUniversidade de Santiago de CompostelaRadboud Universitair Medisch CentrumUniversitair Medisch Centrum GroningenKarolinska InstitutetKing's College LondonLunds UniversitetUniversiteit MaastrichtNational Institute for Health and Care ResearchCentre for Cognitive Ageing and Cognitive EpidemiologyUniversity of OxfordUniversitetssjukhuset ÖrebroRadboud UniversiteitQIMR Berghofer Medical Research InstituteMedical Research CouncilLeids Universitair Medisch CentrumUniversiteit LeidenInstituto de Investigación Sanitaria de Santiago de CompostelaCancer Research UKWellcome TrustMonash UniversityMaastricht Universitair Medisch CentrumRijksuniversiteit GroningenBrigham and Women's Hospital
Mots-clés
Breast cancerGeneOncologyCancerGenetic associationAssociation (psychology)MedicineGeneticsInternal medicineBiologyBioinformaticsGenotypeSingle-nucleotide polymorphismPsychology
Résumé présent dans OpenAlex
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