Lakeman, Inge M. M., van den Broek, Alexandra J., Vos, Julien A. M., Barnes, Daniel R., Adlard, Julian, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert ORCID: 0000-0003-4523-8808, Arun, Banu K., Balmana, Judith, Barrowdale, Daniel, Benitez, Javier, Borg, Ake, Caldes, Trinidad, Caligo, Maria A., Chung, Wendy K., Claes, Kathleen B. M., Collee, J. Margriet, Couch, Fergus J., Daly, Mary B., Dennis, Joe, Dhawan, Mallika, Domchek, Susan M., Eeles, Ros, Engel, Christoph ORCID: 0000-0002-7247-282X, Evans, D. Gareth, Feliubadalo, Lidia ORCID: 0000-0002-1736-0112, Foretova, Lenka ORCID: 0000-0003-0494-2620, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Gayther, Simon A., Gerdes, Anne-Marie, Godwin, Andrew K., Goldgar, David E., Hahnen, Eric, Hake, Christopher R., Hamann, Ute, Hogervorst, Frans B. L., Hooning, Maartje J., Hopper, John L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk ORCID: 0000-0002-6205-6355, Jiao, Yue, John, Esther M., Joseph, Vijai, Karlan, Beth Y., Kets, Carolien M., Konstantopoulou, Irene, Kwong, Ava, Legrand, Clementine, Leslie, Goska, Lesueur, Fabienne, Loud, Jennifer T., Lubinski, Jan, Manoukian, Siranoush, McGuffog, Lesley, Miller, Austin, Gomes, Denise Molina, Montagna, Marco, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Olah, Edith, Olopade, Olufunmilayo I., Park, Sue K., Parsons, Michael T., Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Piedmonte, Marion, Radice, Paolo, Rantala, Johanna, Rennert, Gad, Risch, Harvey A., Schmutzler, Rita K., Sharma, Priyanka, Simard, Jacques ORCID: 0000-0001-6906-3390, Singer, Christian F., Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Teule, Alex, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tung, Nadine, van Rensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Devilee, Peter, van Asperen, Christi J., Bernstein, Jonine L., Offit, Kenneth, Easton, Douglas F., Rookus, Matti A., Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Antoniou, Antonis C., Robson, Mark and Schmidt, Marjanka K. (2021). The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant. Genet. Med., 23 (9). S. 1726 - 1738. LONDON: SPRINGERNATURE. ISSN 1530-0366

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Abstract

Purpose To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lakeman, Inge M. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Broek, Alexandra J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vos, Julien A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barnes, Daniel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adlard, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arason, AdalgeirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, NorbertUNSPECIFIEDorcid.org/0000-0003-4523-8808UNSPECIFIED
Arun, Banu K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balmana, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrowdale, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borg, AkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caligo, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chung, Wendy K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Claes, Kathleen B. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, J. MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mary B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhawan, MallikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domchek, Susan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eeles, RosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Engel, ChristophUNSPECIFIEDorcid.org/0000-0002-7247-282XUNSPECIFIED
Evans, D. GarethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feliubadalo, LidiaUNSPECIFIEDorcid.org/0000-0002-1736-0112UNSPECIFIED
Foretova, LenkaUNSPECIFIEDorcid.org/0000-0003-0494-2620UNSPECIFIED
Friedman, EitanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frost, DebraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganz, Patricia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garber, JudyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gayther, Simon A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerdes, Anne-MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Godwin, Andrew K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldgar, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hake, Christopher R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogervorst, Frans B. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hooning, Maartje J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hulick, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imyanitov, Evgeny N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isaacs, ClaudineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izatt, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
James, Paul A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janavicius, RamunasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen, Uffe BirkUNSPECIFIEDorcid.org/0000-0002-6205-6355UNSPECIFIED
Jiao, YueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joseph, VijaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karlan, Beth Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kets, Carolien M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konstantopoulou, IreneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwong, AvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Legrand, ClementineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leslie, GoskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lesueur, FabienneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loud, Jennifer T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lubinski, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manoukian, SiranoushUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuffog, LesleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miller, AustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gomes, Denise MolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montagna, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mouret-Fourme, EmmanuelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathanson, Katherine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yie, Joanne Ngeow YuenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olah, EdithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olopade, Olufunmilayo I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Sue K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parsons, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Piedmonte, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radice, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rantala, JohannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rennert, GadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Risch, Harvey A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharma, PriyankaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDorcid.org/0000-0001-6906-3390UNSPECIFIED
Singer, Christian F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stadler, ZsofiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoppa-Lyonnet, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutter, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Yen YenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teixeira, Manuel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teo, Soo HwangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teule, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomassen, MadsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thull, Darcy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischkowitz, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tung, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Rensburg, Elizabeth J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vega, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wappenschmidt, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Asperen, Christi J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernstein, Jonine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offit, KennethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rookus, Matti A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robson, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-608432
DOI: 10.1038/s41436-021-01198-7
Journal or Publication Title: Genet. Med.
Volume: 23
Number: 9
Page Range: S. 1726 - 1738
Date: 2021
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1530-0366
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MUTATION CARRIERS; SUSCEPTIBILITY ALLELES; CONSORTIUM; FAMILIES; OVARIANMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60843

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