A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2-Reference-Cited by-同舟云学术

A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2

Published:2023-09-14 Issue: Volume:2023 Page:1-17
ISSN:1098-1004
Container-title:Human Mutation
language:en
Short-container-title:Human Mutation

Author:

Zanti Maria¹^ORCID,O'Mahony Denise G.¹,Parsons Michael T.²,Li Hongyan³,Dennis Joe⁴^ORCID,Aittomäkkiki Kristiina⁵,Andrulis Irene L.⁶⁷,Anton-Culver Hoda⁸,Aronson Kristan J.⁹^ORCID,Augustinsson Annelie¹⁰,Becher Heiko¹¹,Bojesen Stig E.¹²¹³¹⁴,Bolla Manjeet K.⁴,Brenner Hermann¹⁵¹⁶¹⁷,Brown Melissa A.¹⁸,Buys Saundra S.¹⁹,Canzian Federico²⁰,Caputo Sandrine M.²¹²²^ORCID,Castelao Jose E.²³,Chang-Claude Jenny²⁴²⁵,GC-HBOC study Collaborators ²⁶,Czene Kamila²⁷,Daly Mary B.²⁸,De Nicolo Arcangela²⁹,Devilee Peter³⁰³¹,Dörk Thilo³²^ORCID,Dunning Alison M.³³,Dwek Miriam³⁴,Eccles Diana M.³⁵,Engel Christoph³⁶³⁷^ORCID,Evans D. Gareth³⁸³⁹,Fasching Peter A.⁴⁰,Gago-Dominguez Manuela⁴¹,García-Closas Montserrat⁴²,García-Sáenz José A.⁴³,Gentry-Maharaj Aleksandra⁴⁴,Geurts - Giele Willemina R. R.⁴⁵,Giles Graham G.⁴⁶⁴⁷⁴⁸,Glendon Gord⁶,Goldberg Mark S.⁴⁹⁵⁰,Gómez Garcia Encarna B.⁵¹,Güendert Melanie⁵²⁵³⁵⁴,Guénel Pascal⁵⁵,Hahnen Eric²⁶⁵⁶,Haiman Christopher A.⁵⁷,Hall Per²⁷⁵⁸,Hamann Ute⁵⁹,Harkness Elaine F.⁶⁰⁶¹⁶²,Hogervorst Frans B. L.⁶³,Hollestelle Antoinette⁶⁴,Hoppe Reiner⁶⁵⁶⁶,Hopper John L.⁴⁷,Houdayer Claude⁶⁷,Houlston Richard S.⁶⁸,Howell Anthony⁶⁹,ABCTB Investigators ⁷⁰,Jakimovska Milena⁷¹^ORCID,Jakubowska Anna⁷²⁷³,Jernström Helena¹⁰,John Esther M.⁷⁴⁷⁵,Kaaks Rudolf²⁴,Kitahara Cari M.⁷⁶,Koutros Stella⁴²,Kraft Peter⁷⁷⁷⁸,Kristensen Vessela N.⁷⁹⁸⁰,Lacey James V.⁸¹⁸²,Lambrechts Diether⁸³⁸⁴,Léoné Melanie⁸⁵,Lindblom Annika⁸⁶⁸⁷,Lubiński Jan⁷²,Lush Michael⁴,Mannermaa Arto⁸⁸⁸⁹⁹⁰,Manoochehri Mehdi⁵⁹,Manoukian Siranoush⁹¹,Margolin Sara⁵⁸⁹²,Martinez Maria Elena⁹³⁹⁴,Menon Usha⁴⁴^ORCID,Milne Roger L.⁴⁶⁴⁷⁴⁸,Monteiro Alvaro N.⁹⁵,Murphy Rachel A.⁹⁶⁹⁷,Neuhausen Susan L.⁹⁸,Nevanlinna Heli⁹⁹,Newman William G.³⁸³⁹,Offit Kenneth¹⁰⁰¹⁰¹,Park Sue K.¹⁰²¹⁰³¹⁰⁴,James Paul¹⁰⁵¹⁰⁶,Peterlongo Paolo¹⁰⁷,Peto Julian¹⁰⁸,Plaseska-Karanfilska Dijana⁷¹,Punie Kevin¹⁰⁹,Radice Paolo¹¹⁰,Rashid Muhammad U.⁵⁹¹¹¹,Rennert Gad¹¹²,Romero Atocha¹¹³^ORCID,Rosenberg Efraim H.¹¹⁴,Saloustros Emmanouil¹¹⁵^ORCID,Sandler Dale P.¹¹⁶,Schmidt Marjanka K.¹¹⁷¹¹⁸¹¹⁹,Schmutzler Rita K.²⁶⁵⁶¹²⁰,Shu Xiao-Ou¹²¹,Simard Jacques¹²²^ORCID,Southey Melissa C.⁴⁶⁴⁸¹²³,Stone Jennifer⁴⁷¹²⁴,Stoppa-Lyonnet Dominique²¹¹²⁵¹²⁶,Tamimi Rulla M.⁷⁸¹²⁷,Tapper William J.³⁵,Taylor Jack A.¹¹⁶¹²⁸,Teo Soo Hwang¹²⁹¹³⁰,Teras Lauren R.¹³¹,Terry Mary Beth¹³²,Thomassen Mads¹³³,Troester Melissa A.¹³⁴,Vachon Celine M.¹³⁵,Vega Ana¹³⁶¹³⁷¹³⁸,Vreeswijk Maaike P. G.³¹,Wang Qin⁴,Wappenschmidt Barbara²⁶⁵⁶,Weinberg Clarice R.¹³⁹,Wolk Alicja¹⁴⁰¹⁴¹,Zheng Wei¹²¹,Feng Bingjian¹⁴²,Couch Fergus J.¹⁴³,Spurdle Amanda B.²,Easton Douglas F.⁴³³,Goldgar David E.¹⁴²,Michailidou Kyriaki¹⁴^ORCID

Affiliation:

1. Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

2. Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

3. Cancer Control and Population Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

4. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

5. Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

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

7. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

8. Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA

9. Department of Public Health Sciences, and Cancer Research Institute, Queen’s University, Kingston, ON, Canada

10. Oncology, Department of Clinical Sciences in Lund, Lund University, Lund, Sweden

11. Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

12. Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark

13. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark

14. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

15. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

16. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany

17. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

18. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia

19. Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

20. Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany

21. Service de Génétique, Institut Curie, Paris, France

22. Paris Sciences Lettres Research University, Paris, France

23. Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS, Vigo, Spain

24. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

25. Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

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

27. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

28. Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA

29. Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan, Italy

30. Department of Pathology, Leiden University Medical Center, Leiden, Netherlands

31. Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands

32. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany

33. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK

34. School of Life Sciences, University of Westminster, London, UK

35. Faculty of Medicine, University of Southampton, Southampton, UK

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

37. LIFE-Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany

38. Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

39. North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

40. Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany

41. Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain

42. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

43. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain

44. MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK

45. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands

46. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia

47. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

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

49. Department of Medicine, McGill University, Montréal, QC, Canada

50. Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montréal, QC, Canada

51. Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, Netherlands

52. Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany

53. Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany

54. Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

55. Team 'Exposome and Heredity', CESP, Gustave Roussy, INSERM, University Paris-Saclay, UVSQ, Villejuif, France

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

57. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

58. Department of Oncology, Södersjukhuset, Stockholm, Sweden

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

60. Division of Informatics, Imaging and Data Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

61. Nightingale & Genesis Prevention Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK

62. NIHR Manchester Biomedical Research Unit, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK

63. Family Cancer Clinic, The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, Netherlands

64. Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands

65. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany

66. University of Tübingen, Tübingen, Germany

67. Department of Genetics, F76000 and Normandy University, UNIROUEN, Inserm U1245, Normandy Centre for Genomic and Personalized Medicine, Rouen University Hospital, Rouen, France

68. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK

69. Division of Cancer Sciences, University of Manchester, Manchester, UK

70. Australian Breast Cancer Tissue Bank, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia

71. Research Centre for Genetic Engineering and Biotechnology 'Georgi D. Efremov', MASA, Skopje, North Macedonia

72. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland

73. Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland

74. Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA

75. Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

76. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

77. Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA

78. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA

79. Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway

80. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

81. Department of Computational and Quantitative Medicine, City of Hope, Duarte, CA, USA

82. City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA, USA

83. Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium

84. VIB Center for Cancer Biology, VIB, Leuven, Belgium

85. Genetic and Cancer Medical Laboratory HCL-CLB, Hospices Civils de Lyon, Bron, France

86. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

87. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

88. Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland

89. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland

90. Biobank of Eastern Finland, Kuopio University Hospital, Kuopio, Finland

91. Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

92. Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden

93. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA

94. Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA

95. Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA

96. School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada

97. Cancer Control Research, BC Cancer, Vancouver, BC, Canada

98. Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA

99. Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

100. Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

101. Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

102. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

103. Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Republic of Korea

104. Cancer Research Institute, Seoul National University, Seoul, Republic of Korea

105. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia

106. Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Victoria, Australia

107. Genome Diagnostics Program, IFOM-ETS the AIRC Institute of Molecular Oncology, Milan, Italy

108. Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK

109. Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute and University Hospitals Leuven, Leuven, Belgium

110. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy

111. Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan

112. Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel

113. Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain

114. Department of Pathology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, Netherlands

115. Department of Oncology, University Hospital of Larissa, Larissa, Greece

116. Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

117. Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands

118. Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Amsterdam, Netherlands

119. Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands

120. Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

121. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA

122. Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Québec City, QC, Canada

123. Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia

124. Genetic Epidemiology Group, School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia

125. Department of Tumour Biology, INSERM U830, Paris, France

126. Université Paris Descartes, Paris, France

127. Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA

128. Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

129. Breast Cancer Research Programme, Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia

130. Department of Surgery, Faculty of Medicine, University of Malaya, UM Cancer Research Institute, Kuala Lumpur, Malaysia

131. Department of Population Science, American Cancer Society, Atlanta, GA, USA

132. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA

133. Department of Clinical Genetics, Odense University Hospital, Odence C, Denmark

134. Department of Epidemiology, Gillings School of Global Public Health and UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

135. Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA

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

137. Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain

138. Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain

139. Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA

140. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

141. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

142. Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA

143. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

Abstract

A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.

Funder

AECC

Publisher

Hindawi Limited

Subject

Genetics (clinical),Genetics

Link

http://downloads.hindawi.com/journals/humu/2023/9961341.pdf

Reference19 articles.

1. BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance

2. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology

3. Modeling the ACMG/AMP variant classification guidelines as a Bayesian classification framework

4. Integrated Evaluation of DNA Sequence Variants of Unknown Clinical Significance: Application to BRCA1 and BRCA2

5. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model

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