학술논문
A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian and colorectal cancer susceptibility genes.
Document Type
Academic Journal
Author
Makhnoon S; Department of Behavioral Science, UT MD Anderson Cancer Center, Houston, Texas, USA.; Levin B; William G. Rohrer Cancer Genetics Program, Division of Hematology and Medical Oncology, MD Anderson Cancer Center at Cooper University Health Care, Camden, New Jersey, USA.; Ensinger M; OhioHealth Cancer Genetics Program, Columbus, Ohio, USA.; Mattie K; William G. Rohrer Cancer Genetics Program, Division of Hematology and Medical Oncology, MD Anderson Cancer Center at Cooper University Health Care, Camden, New Jersey, USA.; Volk RJ; Department of Health Services Research, UT MD Anderson Cancer Center, Houston, Texas, USA.; Zhao Z; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA.; Mendoza T; Department of Symptoms research, UT MD Anderson Cancer Center, Houston, Texas, USA.; Shete S; Division of Cancer Prevention and Population Sciences, UT MD Anderson Cancer Center, Houston, Texas, USA.; Samiian L; Baptist MD Anderson, Jacksonville, Florida, USA.; Grana G; William G. Rohrer Cancer Genetics Program, Division of Hematology and Medical Oncology, MD Anderson Cancer Center at Cooper University Health Care, Camden, New Jersey, USA.; Grainger A; OhioHealth Cancer Genetics Program, Columbus, Ohio, USA.; Arun B; Clinical Cancer Genetics, UT MD Anderson Cancer Center, Houston, Texas, USA.; Shirts BH; University of Washington, Seattle, WA, USA.; Peterson SK; Department of Behavioral Science, UT MD Anderson Cancer Center, Houston, Texas, USA.
Source
Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences.
Methods: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019.
Results: In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). Compared to their prevalence in the overall sample, reclassification rates for Black individuals were higher (13.6% vs. 19.0%), whereas the rates for Asian individuals were lower (6.3% vs. 3.5%) and rates for White and Hispanic individuals were proportional. Two-year prevalence of VUS reclassification remained steady between 2014 and 2019. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals' clinical managements.
Conclusions: The findings from this large multisite study suggest that VUS reclassification alters clinical management, has implications for precision cancer prevention, and highlights the need for implementing practices and solutions for efficiently returning reinterpreted genetic test results.
(© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Methods: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019.
Results: In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). Compared to their prevalence in the overall sample, reclassification rates for Black individuals were higher (13.6% vs. 19.0%), whereas the rates for Asian individuals were lower (6.3% vs. 3.5%) and rates for White and Hispanic individuals were proportional. Two-year prevalence of VUS reclassification remained steady between 2014 and 2019. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals' clinical managements.
Conclusions: The findings from this large multisite study suggest that VUS reclassification alters clinical management, has implications for precision cancer prevention, and highlights the need for implementing practices and solutions for efficiently returning reinterpreted genetic test results.
(© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)