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Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients

Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL-IGTP-IDIBGI, 08908 Hospitalet de Llobregat, Spain
Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, 08908 Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology, 08908 Hospitalet de Llobregat, Spain
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain
Medical Oncology Department, Catalan Institute of Oncology, IDIBELL, 08908 Hospitalet de Llobregat, Spain
Genomes for Life—GCAT lab Group, Institut Germans Trias i Pujol (IGTP), 08916 Badalona, Spain
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 829;
Received: 7 February 2020 / Revised: 23 March 2020 / Accepted: 25 March 2020 / Published: 30 March 2020
(This article belongs to the Special Issue Molecular Genetics of Breast and Ovary Cancer)
Fanconi anemia (FA) is caused by biallelic mutations in FA genes. Monoallelic mutations in five of these genes (BRCA1, BRCA2, PALB2, BRIP1 and RAD51C) increase the susceptibility to breast/ovarian cancer and are used in clinical diagnostics as bona-fide hereditary cancer genes. Increasing evidence suggests that monoallelic mutations in other FA genes could predispose to tumor development, especially breast cancer. The objective of this study is to assess the mutational spectrum of 14 additional FA genes (FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FANCP, FANCQ, FANCR and FANCU) in a cohort of hereditary cancer patients, to compare with local cancer-free controls as well as GnomAD. A total of 1021 hereditary cancer patients and 194 controls were analyzed using our next generation custom sequencing panel. We identified 35 pathogenic variants in eight genes. A significant association with the risk of breast cancer/breast and ovarian cancer was found for carriers of FANCA mutations (odds ratio (OR) = 3.14 95% confidence interval (CI) 1.4–6.17, p = 0.003). Two patients with early-onset cancer showed a pathogenic FA variant in addition to another germline mutation, suggesting a modifier role for FA variants. Our results encourage a comprehensive analysis of FA genes in larger studies to better assess their role in cancer risk. View Full-Text
Keywords: Breast cancer risk; Breast and ovarian cancer risk; Fanconi Anemia; Hereditary Cancer; NGS panel sequencing Breast cancer risk; Breast and ovarian cancer risk; Fanconi Anemia; Hereditary Cancer; NGS panel sequencing
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del Valle, J.; Rofes, P.; Moreno-Cabrera, J.M.; López-Dóriga, A.; Belhadj, S.; Vargas-Parra, G.; Teulé, À.; Cuesta, R.; Muñoz, X.; Campos, O.; Salinas, M.; de Cid, R.; Brunet, J.; González, S.; Capellá, G.; Pineda, M.; Feliubadaló, L.; Lázaro, C. Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients. Cancers 2020, 12, 829.

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