American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology

, volume 40 , issue 14 , pages 1529-1541

Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

Shuai Li ^{1, 2, 3}

Valentina Silvestri ⁴

Goska Leslie ²

Timothy R. Rebbeck ^{5, 6}

Susan J. Ramus ⁷

J. HOPPER ¹

Henriette Roed Nielsen ⁸

Andrew Lee ²

Xin Yang ²

Lesley Mcguffog ²

MICHAEL F. PARSONS ⁹

I Andrulis ^{10, 11}

Norbert Arnold ^{12, 13}

Muriel Belotti ^{14, 15}

Åke Borg ¹⁶

Bruno Buecher ^{14, 15}

Saundra S Buys ¹⁷

Sandrine M. Caputo ^{14, 15}

Wendy K. Chung ¹⁸

Chrystelle Colas ^{14, 15}

Sarah V Colonna ¹⁷

Jackie Cook ¹⁹

Mary B. Daly ²⁰

Miguel Hoya ²¹

Antoine de Pauw ^{14, 15}

Hélène Delhomelle ^{14, 15}

Jacqueline Eason ²²

C. J. Engel ²³

D. Gareth Evans ^{24, 25}

Ulrike Faust ²⁶

Tanja N. Fehm ²⁷

Florentia Fostira ²⁸

George Fountzilas ^{29, 30}

Megan N Frone ³¹

Vanesa García Barberán ²¹

Vanesa Garcia-Barberan ²¹

Pilar Garre ²¹

Marion Gauthier Villars ^{14, 15}

Marion Gauthier-Villars ^{14, 15}

Andrea Gehrig ³²

Gord Glendon ¹⁰

D. Goldgar ³³

L. Golmard ^{14, 15}

Mark H. Greene ³¹

Eric Hahnen ^{34, 35}

Ute Hamann ³⁶

Helen Hanson ³⁷

Tiara Hassan ³⁸

Julia Hentschel ³⁹

Judit Horváth ⁴⁰

Judit Horvath ⁴⁰

Louise Izatt ⁴¹

Ramunas Janavicius ^{42, 43}

Yue Jiao ^{44, 45, 46}

E John ^{47, 48}

Beth Y. Karlan ⁴⁹

SUNG-WON KIM ⁵⁰

I. Konstantopoulou ²⁸

Ava Kwong ^{51, 52, 53}

Anthony Laugé ^{14, 15}

Jong Won Lee ⁵⁴

Fabienne Lesueur ^{44, 45, 46}

Noura Mebirouk ^{44, 45, 46}

Alfons Meindl ^{55, 56}

Emmanuelle Mouret Fourme ^{14, 15}

Emmanuelle Mouret-Fourme ^{14, 15}

Hannah Musgrave ⁵⁷

Joanne Ngeow ^{58, 59}

Dieter Niederacher ²⁷

Sue K. Park ^{60, 61, 62}

Inge Søkilde Pedersen ^{63, 64, 65}

Juliane Ramser ⁵⁶

Susan J. Ramus ^{66, 67}

Johanna Rantala ⁶⁸

Muhammad U. Rashid ^{36, 69}

Florian Reichl ⁷⁰

Julia Ritter ⁷¹

Andreas Rump ⁷²

Marta Santamariña ^{73, 74, 75}

Claire Saule ^{14, 15}

Gunnar Schmidt ⁷⁶

Rita K. Schmutzler ^{34, 35, 77}

Leigha Senter ⁷⁸

Saba Sharif ⁷⁹

Christian F. Singer ⁷⁰

Melissa C Southey ^{3, 80, 81}

Dominique Stoppa-Lyonnet ^{14, 82, 83}

Christian Sutter ⁸⁴

Yen Tan ⁷⁰

Soo-Hwang Teo ^{38, 85}

Mary Beth Terry ⁸⁶

Mads Thomassen ⁸

M. Tischkowitz ^{87, 88}

Amanda E. Toland ⁸⁹

Diana Torres ^{36, 90}

Ana Lydia Vega ^{73, 74, 75}

Sebastian A Wagner ⁹¹

Shan Wang-Gohrke ⁹²

Barbara Wappenschmidt ^{34, 35}

Bernhard H.F. Weber ^{93, 94}

Drakoulis Yannoukakos ²⁸

Amanda B Spurdle ⁹

Douglas F. Easton ²

Georgia Chenevix-Trench ⁹

L. Ottini ⁴

Antonis C. Antoniou ²

Hide authors affiliations Show authors affiliations: 94 affiliations

Center for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia |

Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom |

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia

Monash University

Monash Health

⁴

Department Of Molecular Medicine, Sapienza University of Rome, Rome, Italy |

⁵

Harvard T.H. Chan School of Public Health, Boston, MA |

⁶

Dana-Farber Cancer institute, Boston, MA |

⁷

Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA |

⁸

Department of Clinical Genetics, Odense University Hospital, Odence, Denmark |

⁹

Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia |

¹⁰

Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada |

¹¹

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada |

¹²

Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany |

¹³

Institute of Clinical Molecular Biology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany |

¹⁴

Service de Génétique, Institut Curie, Paris, France |

¹⁵

Paris Sciences Lettres Research University, Paris, France |

¹⁶

Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden |

¹⁷

Department of Medicine and Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT

Huntsman Cancer Institute

University of Utah Health

¹⁸

Departments of Pediatrics and Medicine, Columbia University, New York, NY |

¹⁹

Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom |

²⁰

Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA |

²¹

Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clinico San Carlos), Madrid, Spain

Centro de Investigación Biomédica en Red de Cáncer

Health Research Institute of the Hospital Clínico San Carlos

²²

Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom |

²³

Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany |

²⁴

Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Center, Manchester, United Kingdom

University of Manchester

Manchester Academic Health Science Centre

²⁵

North West Genomics Laboratory Hub, Manchester Center for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, United Kingdom

Manchester University NHS Foundation Trust

Manchester Academic Health Science Centre

²⁶

Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany |

²⁷

Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany |

²⁸

Molecular Diagnostics Laboratory, INRASTES, National Center for Scientific Research “Demokritos”, Athens, Greece |

²⁹

Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece |

³⁰

Department of Medical Oncology, German Oncology Center, Limassol, Cyprus |

³¹

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD |

³²

Department of Human Genetics, University Würzburg, Würzburg, Germany |

³³

Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT |

³⁴

Center for Familial Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany |

³⁵

Center for Integrated Oncology (CIO), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany |

³⁶

Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany |

³⁷

Southwest Thames Regional Genetics Service, St George's Hospital, London, United Kingdom |

³⁸

Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia |

³⁹

Institute of Human Genetics, University Hospital Leipzig, Leipzig, Germany |

⁴⁰

Institute of Human Genetics, University of Münster, Münster, Germany |

⁴¹

Clinical Genetics Department, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom |

⁴²

Faculty of Medicine, Department of Human and Medical Genetics, Institute of Biomedical Sciences, Vilnius University, Vilnius, Lithuania |

⁴³

State Research Institute Center for Innovative Medicine, Vilnius, Lithuania |

⁴⁴

Genetic Epidemiology of Cancer team, Inserm U900, Paris, France |

⁴⁵

Institut curie, Paris, France |

⁴⁶

MINES ParisTech, Fontainebleau, France |

⁴⁷

Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA |

⁴⁸

Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA |

⁴⁹

Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA |

⁵⁰

Department of Surgery, Daerim Saint Mary's Hospital, Seoul, South Korea |

⁵¹

Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong |

⁵²

Department of Surgery, the University of Hong Kong, Hong Kong |

⁵³

Department of Surgery and Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong |

⁵⁴

Department of Surgery, Ulsan University College of Medicine and Asan Medical Center, Seoul, South Korea |

⁵⁵

Department of Gynecology and Obstetrics, University of Munich, Campus Großhadern, Munich, Germany |

⁵⁶

Division of Gynaecology and Obstetrics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany

Ludwig Maximilian University of Munich

Rechts der Isar Hospital

⁵⁷

Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom |

⁵⁸

Cancer Genetics Service, National Cancer Center, Singapore, Singapore |

⁵⁹

Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore |

⁶⁰

Department of Preventive Medicine, Seoul National University College of medicine, Seoul, South Korea |

⁶¹

Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, South Korea |

⁶²

Cancer Research Institute, Seoul National University, Seoul, South Korea |

⁶³

Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark |

⁶⁴

Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark |

⁶⁵

Department of Clinical Medicine, Aalborg University, Aalborg, Denmark |

⁶⁶

Faculty of Medicine, School of Women's and Children's Health, University of NSW Sydney, Sydney, New South Wales, Australia |

⁶⁷

Adult Cancer Program, Lowy Cancer Research Center, University of NSW Sydney, Sydney, New South Wales, Australia |

⁶⁸

Clinical Genetics, Karolinska Institutet, Stockholm, Sweden |

⁶⁹

Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH & RC), Lahore, Pakistan |

⁷⁰

Department of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria |

⁷¹

Institute of Medical and Human Genetics, Charité–Universitätsmedizin Berlin, Berlin, Germany |

⁷²

Faculty of Medicine Carl Gustav Carus, Institute for Clinical Genetics, TU Dresden, Dresden, Germany

Technische Universität Dresden

University Hospital Carl Gustav Carus

⁷³

Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain |

⁷⁴

Fundación Pública Galega Medicina Xenómica, Santiago De Compostela, Spain |

⁷⁵

Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain |

⁷⁶

Institute of Human Genetics, Hannover Medical School, Hannover, Germany |

⁷⁷

Faculty of Medicine, Center for Molecular Medicine Cologne (CMMC), University Hospital Cologne, University of Cologne, Cologne, Germany |

⁷⁸

Clinical Cancer Genetics Program, Division of Human Genetics, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, OH |

⁷⁹

West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Birmingham, United Kingdom |

⁸⁰

Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia |

⁸¹

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia |

⁸²

Department of Tumour Biology, INSERM U830, Paris, France |

⁸³

Université Paris Descartes, Paris, France |

⁸⁴

Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany |

⁸⁵

Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia |

⁸⁶

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY |

⁸⁷

Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montréal, QC, Canada |

⁸⁸

Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom |

⁸⁹

Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH |

⁹⁰

Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia |

⁹¹

Department of Medicine, Hematology/Oncology, Goethe-University Frankfurt, Frankfurt, Germany |

⁹²

Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany |

⁹³

Institute of Human Genetics, University Regensburg, Regensburg, Germany |

⁹⁴

Institute of Clinical Human Genetics, University Hospital Regensburg, Regensburg, Germany |

Publication type: Journal Article

Publication date: 2022-05-10

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology

scimago Q1

wos Q1

SJR: 11.205

CiteScore: 38.9

Impact factor: 41.9

ISSN: 0732183X, 15277755

DOI: 10.1200/jco.21.02112

Copy DOI

PubMed ID: 35077220

Cancer Research

Oncology

Abstract

PURPOSE

To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.

METHODS

We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment.

RESULTS

BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers.

CONCLUSION

In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.

Found

1 citation

Rump Andreas

47 publications, 1 707 citations, 1 review

h-index: 21

Novo Nordisk

University of Copenhagen

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GOST Copy

Li S. et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants // Journal of Clinical Oncology. 2022. Vol. 40. No. 14. pp. 1529-1541.

GOST all authors (up to 50) Copy

Li S. et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants // Journal of Clinical Oncology. 2022. Vol. 40. No. 14. pp. 1529-1541.

RIS |

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BibTex (up to 50 authors) Copy

@article{2022_Li,

author = {Shuai Li and Valentina Silvestri and Goska Leslie and Timothy R. Rebbeck and Susan J. Ramus and J. HOPPER and Henriette Roed Nielsen and Andrew Lee and Xin Yang and Lesley Mcguffog and MICHAEL F. PARSONS and I Andrulis and Norbert Arnold and Muriel Belotti and Åke Borg and Bruno Buecher and Saundra S Buys and Sandrine M. Caputo and Wendy K. Chung and Chrystelle Colas and Sarah V Colonna and Jackie Cook and Mary B. Daly and Miguel Hoya and Antoine de Pauw and Hélène Delhomelle and Jacqueline Eason and C. J. Engel and D. Gareth Evans and Ulrike Faust and Tanja N. Fehm and Florentia Fostira and George Fountzilas and Megan N Frone and Vanesa García Barberán and Vanesa Garcia-Barberan and Pilar Garre and Marion Gauthier Villars and Marion Gauthier-Villars and Andrea Gehrig and Gord Glendon and D. Goldgar and L. Golmard and Mark H. Greene and Eric Hahnen and Ute Hamann and Helen Hanson and Tiara Hassan and Julia Hentschel and Judit Horváth and others},

title = {Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants},

journal = {Journal of Clinical Oncology},

year = {2022},

volume = {40},

publisher = {American Society of Clinical Oncology (ASCO)},

month = {may},

url = {https://ascopubs.org/doi/10.1200/JCO.21.02112},

number = {14},

pages = {1529--1541},

doi = {10.1200/jco.21.02112}

}

MLA

Cite this

MLA Copy

Li, Shuai, et al. “Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.” Journal of Clinical Oncology, vol. 40, no. 14, May. 2022, pp. 1529-1541. https://ascopubs.org/doi/10.1200/JCO.21.02112.

Publisher

American Society of Clinical Oncology (ASCO)

Journal

Journal of Clinical Oncology

scimago Q1

wos Q1

SJR

11.205

CiteScore

38.9

Impact factor

41.9

ISSN

0732183X (Print)

15277755 (Electronic)

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