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DOI 10.1038/s41436-021-01198-7

Медицинская библиотека · Genetics in medicine : official journal of the American College of Medical Genetics · 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.

Lakeman Inge M M, van den Broek Alexandra J, Vos Juliën A M, Barnes Daniel R, Adlard Julian, Andrulis Irene L, Arason Adalgeir, Arnold Norbert, Arun Banu K, Balmaña Judith, Barrowdale Daniel, Benitez Javier, Borg Ake, Caldés Trinidad, Caligo Maria A, Chung Wendy K, Claes Kathleen B M, GEMO Study Collaborators, EMBRACE Collaborators, Collée J Margriet, Couch Fergus J, Daly Mary B, Dennis Joe, Dhawan Mallika, Domchek Susan M, Eeles Ros, Engel Christoph, Evans D Gareth, Feliubadaló Lidia, Foretova Lenka, 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, OCGN Investigators, HEBON Investigators, KconFab Investigators, Isaacs Claudine, Izatt Louise, Jakubowska Anna, James Paul A, Janavicius Ramunas, Jensen Uffe Birk, Jiao Yue, John Esther M, Joseph Vijai, Karlan Beth Y, Kets Carolien M, Konstantopoulou Irene, Kwong Ava, Legrand Clémentine, Leslie Goska, Lesueur Fabienne, Loud Jennifer T, Lubiński 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, Piedmonte Marion, Radice Paolo, Rantala Johanna, Rennert Gad, Risch Harvey A, Schmutzler Rita K, Sharma Priyanka, Simard Jacques, Singer Christian F, Stadler Zsofia, Stoppa-Lyonnet Dominique, Sutter Christian, Tan Yen Yen, Teixeira Manuel R, Teo Soo Hwang, Teulé 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, Antoniou Antonis C, Robson Mark, Schmidt Marjanka K

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: Lakeman Inge M M, van den Broek Alexandra J, Vos Juliën A M, Barnes Daniel R, Adlard Julian, Andrulis Irene L, Arason Adalgeir, Arnold Norbert, Arun Banu K, Balmaña Judith, Barrowdale Daniel, Benitez Javier, Borg Ake, Caldés Trinidad, Caligo Maria A, Chung Wendy K, Claes Kathleen B M, GEMO Study Collaborators, EMBRACE Collaborators, Collée J Margriet, Couch Fergus J, Daly Mary B, Dennis Joe, Dhawan Mallika, Domchek Susan M, Eeles Ros, Engel Christoph, Evans D Gareth, Feliubadaló Lidia, Foretova Lenka, 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, OCGN Investigators, HEBON Investigators, KconFab Investigators, Isaacs Claudine, Izatt Louise, Jakubowska Anna, James Paul A, Janavicius Ramunas, Jensen Uffe Birk, Jiao Yue, John Esther M, Joseph Vijai, Karlan Beth Y, Kets Carolien M, Konstantopoulou Irene, Kwong Ava, Legrand Clémentine, Leslie Goska, Lesueur Fabienne, Loud Jennifer T, Lubiński 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, Piedmonte Marion, Radice Paolo, Rantala Johanna, Rennert Gad, Risch Harvey A, Schmutzler Rita K, Sharma Priyanka, Simard Jacques, Singer Christian F, Stadler Zsofia, Stoppa-Lyonnet Dominique, Sutter Christian, Tan Yen Yen, Teixeira Manuel R, Teo Soo Hwang, Teulé 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, Antoniou Antonis C, Robson Mark, Schmidt Marjanka K. 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.. Genetics in medicine : official journal of the American College of Medical Genetics. 2021. DOI: 10.1038/s41436-021-01198-7.

Предметные рубрики MeSH

AdultBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsFemaleGenetic Predisposition to DiseaseHeterozygoteHumansMutationRetrospective StudiesRisk Factors
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