Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • GEMO Study Collaborators - (Autor:in)
  • Institut für Klinische Genetik
  • University of Cambridge
  • University of Rome La Sapienza
  • Chapel Allerton Hospital
  • Landspitali University Hospital
  • Great Ormond Street Hospital for Children NHS Trust
  • University of Helsinki
  • Lunenfeld-Tanenbaum Research Institute
  • Christian-Albrechts-Universität zu Kiel (CAU)
  • Leibniz Universität Hannover (LUH)
  • Unit of Medical Genetics
  • Vall d'Hebron Institute of Oncology (VHIO)
  • University Hospitals of Leicester NHS Trust
  • Institut Curie
  • Biomedical Network on Rare Diseases (CIBERER)
  • Département de Biopathologie
  • Universitätsklinikum Odense
  • Lund University
  • National Institute of Oncology
  • London North West University Healthcare NHS Trust
  • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • Royal Devon and Exeter Hospital
  • Bellvitge Biomedical Research Institute (IDIBELL)
  • University of Utah Hospital
  • Hospital Clinico Universitario San Carlos
  • Basurto University Hospital
  • Peter MacCallum Cancer Center
  • Ohio State University
  • Division of Functional Onco-Genomics and Genetics
  • Ghent University
  • Sheffield Children's Hospital
  • University of Modena and Reggio Emilia
  • University of Udine
  • South Glasgow University Hospitals
  • National Cancer Centre


BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.

METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.

RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.

CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.


Seiten (von - bis)109-122
FachzeitschriftJournal of the National Cancer Institute
PublikationsstatusVeröffentlicht - 28 Juli 2021

Externe IDs

PubMedCentral PMC8755508
Scopus 85122613384
unpaywall 10.1093/jnci/djab147
Mendeley 6e84d5f2-57fc-37da-9d16-b75418503baf


Ziele für nachhaltige Entwicklung


  • Aged, 80 and over, BRCA1 Protein/genetics, BRCA2 Protein/genetics, Breast Neoplasms/epidemiology, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Mutation, Polymorphism, Single Nucleotide, Prostatic Neoplasms/epidemiology, Risk Assessment, Risk Factors