Abstract
In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients’ representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the “actionability” of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.
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Acknowledgements
We thank the patient associations BRCA France, Vaincre les Maladies Lysosomales, and APTEF Familial polyposis for their involvement. No industry or corporate sponsors contributed to the development of these recommendations. SFMPP is not funded by industrial or commercial companies but by grants from public. We thank public institutions such as the French National Cancer Institute (“Institut National du Cancer”, INCa) and, the French Foundation for Cancer Research (“Association pour la Recherche sur le Cancer”, ARC), and territorial community support (by the “Metropole of Montpellier” and the “Region Occitanie”). for donations supporting SFMPP annual meeting. Communication of the recommendations to the medical and scientific society took place in an independent framework of industrial actors, at the annual 4th SFMPP congress in Paris (June 2017).
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The authors declare no conflicts of interest with industry or firms commercializing genetic tests. No industry or corporate sponsors contributed to the development of these recommendations. SFMPP is not funded by industrial or commercial companies but by grants from public institutions and partially self-funded by SFMPP annual congresses. Dr. Pujol discloses attending Advisory Board Membership meetings for AstraZeneca, Pfizer, and Genomic Health.
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Flowchart representing the evaluation process and ranking of the initial cancer related gene list by the medical workgroup of the SFMPP
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Pujol, P., Vande Perre, P., Faivre, L. et al. Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations. Eur J Hum Genet 26, 1732–1742 (2018). https://doi.org/10.1038/s41431-018-0224-1
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DOI: https://doi.org/10.1038/s41431-018-0224-1
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