Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Hongyan Li¹, Christoph Engel², Miguel de la Hoya³, Paolo Peterlongo⁴, Drakoulis Yannoukakos⁵, Luca Livraghi⁶, Paolo Radice⁷, Mads Thomassen⁸, Thomas V O Hansen⁹, Anne-Marie Gerdes⁹, Henriette R Nielsen¹⁰, Sandrine M Caputo¹¹, Alberto Zambelli¹², Ake Borg¹³, Angela Solano¹⁴, Abigail Thomas¹⁵, Michael T Parsons¹⁶, Antonis C Antoniou¹⁷, Goska Leslie¹⁷, Xin Yang¹⁷, Georgia Chenevix-Trench¹⁶, Trinidad Caldes³, Ava Kwong¹⁸, Inge Søkilde Pedersen¹⁹, Charlotte K Lautrup²⁰, Esther M John²¹, Mary Beth Terry²², John L Hopper²³, Melissa C Southey²⁴, Irene L Andrulis²⁵, Marc Tischkowitz²⁶, Ramunas Janavicius²⁷, Susanne E Boonen⁸, Lone Kroeldrup⁸, Liliana Varesco²⁸, Ute Hamann²⁹, Ana Vega³⁰, Edenir I Palmero³¹, Judy Garber³², Marco Montagna³³, Christi J Van Asperen³⁴, Lenka Foretova³⁵, Mark H Greene³⁶, Tina Selkirk³⁷, Pal Moller³⁸, Amanda E Toland³⁹, Susan M Domchek⁴⁰, Paul A James⁴¹, Heather Thorne⁴², Diana M Eccles⁴³, Sarah M Nielsen⁴⁴, Siranoush Manoukian⁴⁵, Barbara Pasini⁴⁶, Maria A Caligo⁴⁷, Conxi Lazaro⁴⁸, Judy Kirk⁴⁹, Barbara Wappenschmidt⁵⁰, Amanda B Spurdle¹⁶, Fergus J Couch⁵¹, Rita Schmutzler⁵⁰, David E Goldgar⁵²; ENIGMA Consortium; CIMBA Consortium

Affiliations

¹ Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
² Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.
³ Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain.
⁴ Genome Diagnostics Program, IFOM - the FIRC Institute of Molecular Oncology, Milan, Italy.
⁵ Molecular Diagnostics Laboratory, National Centre for Scientific Research "Demokritos", INRASTES Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, Athens, Greece.
⁶ Medical Oncology Unit, AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII, Bergamo, Italy; University of Siena, Siena, Italy.
⁷ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
⁸ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
⁹ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁰ Department of Clinical Genetics Sygehus Lillebaelt, Vejle Hospital, Vejle, Denmark.
¹¹ Service de Génétique, Institut Curie, Paris, France; Paris Sciences and Lettres Research University, Paris, France.
¹² Medical Oncology Unit, AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII, Bergamo, Italy.
¹³ Divisions of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
¹⁴ INBIOMED, Faculty of Medicine, University of Buenos Aires, CONICET and Genotyping Laboratory, Department of Clinical Chemistry, CEMIC, Buenos Aires, Argentina.
¹⁵ Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
¹⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
¹⁸ Cancer Genetics Centre, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong; Department of Surgery, LKS Faculty of Medicine,University of Hong Kong, Pok Fu Lam, Hong Kong.
¹⁹ Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center and Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, The Faculty of Medicine, Aalborg University of Aalborg, Aalborg, Denmark.
²⁰ Clinical Cancer Research Center and Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, The Faculty of Medicine, Aalborg University of Aalborg, Aalborg, Denmark.
²¹ Department of Epidemiology & Population Health and Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA.
²² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY.
²³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
²⁴ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Clinical Pathology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
²⁵ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
²⁶ Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Cambridge, United Kingdom.
²⁷ Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
²⁸ Unit of Hereditary Cancer, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
²⁹ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³⁰ Fundación Pública galega Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain.
³¹ Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil; National Cancer Institute, Rio de Janeiro, Brazil.
³² Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA.
³³ Immunology and Molecular Oncology Unit, IOV - Istituto Oncologico Veneto - IRCCS, Padova, Italy.
³⁴ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
³⁵ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
³⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
³⁷ NorthShore University HealthSystem, University of Chicago, Evanston, IL.
³⁸ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Center for Hereditary Tumors, HELIOS-Klinikum Wuppertal, University of Witten-Herdecke, Wuppertal, Germany.
³⁹ Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH.
⁴⁰ Basser Center for BRCA, Abramson Cancer Center, Penn Medicine, University of Pennsylvania, Philadelphia, PA.
⁴¹ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
⁴² The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
⁴³ Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
⁴⁴ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL.
⁴⁵ Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
⁴⁶ Medical Genetics Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
⁴⁷ SOD Genetica Molecolare, University Hospital, Pisa, Italy.
⁴⁸ ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Hereditary Cancer Program, Catalan Institute of Oncology, Barcelona, Spain.
⁴⁹ Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney Medical School, University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
⁵⁰ Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine, University of Cologne, Cologne, Germany.
⁵¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
⁵² Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT. Electronic address: david.goldgar@hsc.utah.edu.

PMID: 34906479
PMCID: PMC10170303
DOI: 10.1016/j.gim.2021.08.016

Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Hongyan Li et al. Genet Med. 2022 Jan.

. 2022 Jan;24(1):119-129.

doi: 10.1016/j.gim.2021.08.016. Epub 2021 Nov 30.

Authors

Affiliations

¹ Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
² Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.
³ Molecular Oncology Laboratory, CIBERONC, Hospital Clinico San Carlos, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain.
⁴ Genome Diagnostics Program, IFOM - the FIRC Institute of Molecular Oncology, Milan, Italy.
⁵ Molecular Diagnostics Laboratory, National Centre for Scientific Research "Demokritos", INRASTES Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, Athens, Greece.
⁶ Medical Oncology Unit, AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII, Bergamo, Italy; University of Siena, Siena, Italy.
⁷ Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
⁸ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
⁹ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁰ Department of Clinical Genetics Sygehus Lillebaelt, Vejle Hospital, Vejle, Denmark.
¹¹ Service de Génétique, Institut Curie, Paris, France; Paris Sciences and Lettres Research University, Paris, France.
¹² Medical Oncology Unit, AZIENDA SOCIO SANITARIA TERRITORIALE PAPA GIOVANNI XXIII, Bergamo, Italy.
¹³ Divisions of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
¹⁴ INBIOMED, Faculty of Medicine, University of Buenos Aires, CONICET and Genotyping Laboratory, Department of Clinical Chemistry, CEMIC, Buenos Aires, Argentina.
¹⁵ Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
¹⁶ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
¹⁷ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
¹⁸ Cancer Genetics Centre, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong; Department of Surgery, LKS Faculty of Medicine,University of Hong Kong, Pok Fu Lam, Hong Kong.
¹⁹ Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark; Clinical Cancer Research Center and Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, The Faculty of Medicine, Aalborg University of Aalborg, Aalborg, Denmark.
²⁰ Clinical Cancer Research Center and Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, The Faculty of Medicine, Aalborg University of Aalborg, Aalborg, Denmark.
²¹ Department of Epidemiology & Population Health and Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA.
²² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY.
²³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
²⁴ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia; Department of Clinical Pathology, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
²⁵ Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
²⁶ Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Cambridge, United Kingdom.
²⁷ Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
²⁸ Unit of Hereditary Cancer, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
²⁹ Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³⁰ Fundación Pública galega Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain.
³¹ Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil; National Cancer Institute, Rio de Janeiro, Brazil.
³² Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA.
³³ Immunology and Molecular Oncology Unit, IOV - Istituto Oncologico Veneto - IRCCS, Padova, Italy.
³⁴ Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
³⁵ Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
³⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
³⁷ NorthShore University HealthSystem, University of Chicago, Evanston, IL.
³⁸ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Center for Hereditary Tumors, HELIOS-Klinikum Wuppertal, University of Witten-Herdecke, Wuppertal, Germany.
³⁹ Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH.
⁴⁰ Basser Center for BRCA, Abramson Cancer Center, Penn Medicine, University of Pennsylvania, Philadelphia, PA.
⁴¹ Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
⁴² The Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
⁴³ Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
⁴⁴ Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL.
⁴⁵ Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
⁴⁶ Medical Genetics Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
⁴⁷ SOD Genetica Molecolare, University Hospital, Pisa, Italy.
⁴⁸ ONCOBELL-IDIBELL-IDIBGI-IGTP, CIBERONC, Hereditary Cancer Program, Catalan Institute of Oncology, Barcelona, Spain.
⁴⁹ Familial Cancer Service, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney Medical School, University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Westmead, New South Wales, Australia.
⁵⁰ Center for Hereditary Breast and Ovarian Cancer, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO), Faculty of Medicine, University of Cologne, Cologne, Germany.
⁵¹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
⁵² Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT. Electronic address: david.goldgar@hsc.utah.edu.

PMID: 34906479
PMCID: PMC10170303
DOI: 10.1016/j.gim.2021.08.016

Erratum in

Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants.
Li H, Engel C, Hoya M, Peterlongo P, Yannoukakos D, Livraghi L, Radice P, Thomassen M, Hansen TVO, Gerdes AM, Nielsen HR, Caputo SM, Zambelli A, Borg A, Solano A, Thomas A, Parsons MT, Antoniou AC, Leslie G, Yang X, Chenevix-Trench G, Caldes T, Kwong A, Pedersen IS, Lautrup CK, John EM, Terry MB, Hopper JL, Southey MC, Andrulis IL, Tischkowitz M, Janavicius R, Boonen SE, Kroeldrup L, Varesco L, Hamann U, Vega A, Palmero EI, Garber J, Montagna M, Van Asperen CJ, Foretova L, Greene MH, Selkirk T, Moller P, Toland AE, Domchek SM, James PA, Thorne H, Eccles DM, Nielsen SM, Manoukian S, Pasini B, Caligo MA, Lazaro C, Kirk J, Wappenschmidt B, Spurdle AB, Couch FJ, Schmutzler R, Goldgar DE; ENIGMA Consortium and CIMBA Consortium. Li H, et al. Genet Med. 2022 Oct;24(10):2208. doi: 10.1016/j.gim.2022.08.005. Genet Med. 2022. PMID: 36205748 No abstract available.

Abstract

Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants.

Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis.

Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P = .01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P = .005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs.

Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes.

Keywords: BRCA1; BRCA2; Cancer risks; Missense variants.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest F.J.C. has received consulting fees from Astrazeneca. A.S. has received consulting fees from Pfizer and Astra Zeneca. T.V.O.H. has received honoraria from Pfizer. All other authors declare no conflicts of interest.

References

1. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995;56(1):265–271. - PMC - PubMed
1. Antoniou AC, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117–1130. Published correction appears in Am J Hum Genet. 2003;73(3):709. 10.1086/375033. - DOI - PMC - PubMed
1. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402–2416. 10.1001/jama.2017.7112. - DOI - PubMed
1. Thompson D, Easton D, Breast Cancer Linkage Consortium. Variation in BRCA1 cancer risks by mutation position. Cancer Epidemiol Biomarkers Prev. 2002;11(4):329–336. - PubMed
1. Gayther SA, Warren W, Mazoyer S, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet. 1995;11(4):428–433. 10.1038/ng1295-428. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Affiliations

Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous