Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores. / GEMO Study Collaborators; EMBRACE Collaborators; kConFab Investigators; HEBON Investigators; BRCA1; BRCA2.
I: National Cancer Institute. Journal (Online), Bind 114, Nr. 1, 147, 01.2022, s. 109-122.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
AU - Barnes, Daniel R.
AU - Silvestri, Valentina
AU - Leslie, Goska
AU - McGuffog, Lesley
AU - Dennis, Joe
AU - Yang, Xin
AU - Adlard, Julian
AU - Agnarsson, Bjarni A.
AU - Ahmed, Munaza
AU - Aittomaki, Kristiina
AU - Andrulis, Irene L.
AU - Arason, Adalgeir
AU - Arnold, Norbert
AU - Auber, Bernd
AU - Azzollini, Jacopo
AU - Balmana, Judith
AU - Barkardottir, Rosa B.
AU - Barrowdale, Daniel
AU - Barwell, Julian
AU - Belotti, Muriel
AU - Benitez, Javier
AU - Berthet, Pascaline
AU - Boonen, Susanne E.
AU - Borg, Ake
AU - Bozsik, Aniko
AU - Brady, Angela F.
AU - Brennan, Paul
AU - Brewer, Carole
AU - Brunet, Joan
AU - Bucalo, Agostino
AU - Buys, Saundra S.
AU - Caldes, Trinidad
AU - Caligo, Maria A.
AU - Campbell, Ian
AU - Cassingham, Hayley
AU - Christensen, Lise Lotte
AU - Cini, Giulia
AU - Claes, Kathleen B. M.
AU - Cook, Jackie
AU - Coppa, Anna
AU - Cortesi, Laura
AU - Damante, Giuseppe
AU - Darder, Esther
AU - Davidson, Rosemarie
AU - de la Hoya, Miguel
AU - De Leeneer, Kim
AU - de Putter, Robin
AU - Del Valle, Jesus
AU - Diez, Orland
AU - Hansen, Thomas V. O.
AU - GEMO Study Collaborators
AU - EMBRACE Collaborators
AU - kConFab Investigators
AU - HEBON Investigators
AU - BRCA1
AU - BRCA2
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - MUTATION CARRIERS
KW - ASSOCIATION
KW - OVARIAN
U2 - 10.1093/jnci/djab147
DO - 10.1093/jnci/djab147
M3 - Journal article
C2 - 34320204
VL - 114
SP - 109
EP - 122
JO - National Cancer Institute. Journal (Online)
JF - National Cancer Institute. Journal (Online)
SN - 1460-2105
IS - 1
M1 - 147
ER -
ID: 314166901