Le, Marchand L
van, den, Ouweland, AMW
van Veen, EM
AffiliationGynaecology Research Unit, Hannover Medical School, Hannover, Germany
MetadataShow full item record
AbstractFanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p?=?0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
CitationDork T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al. Two truncating variants in FANCC and breast cancer risk. Sci Rep. 2019 Aug 29;9(1):12524.
- Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients.
- Authors: Del Valle J, Rofes P, Moreno-Cabrera JM, 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
- Issue date: 2020 Mar 30
- The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.
- Authors: Barroso E, Pita G, Arias JI, Menendez P, Zamora P, Blanco M, Benitez J, Ribas G
- Issue date: 2009 Dec
- Evaluation of Fanconi Anemia genes in familial breast cancer predisposition.
- Authors: Seal S, Barfoot R, Jayatilake H, Smith P, Renwick A, Bascombe L, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N, Breast Cancer Susceptibility Collaboration.
- Issue date: 2003 Dec 15
- Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients.
- Authors: Lhota F, Zemankova P, Kleiblova P, Soukupova J, Vocka M, Stranecky V, Janatova M, Hartmannova H, Hodanova K, Kmoch S, Kleibl Z
- Issue date: 2016 Oct
- Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals.
- Authors: Kuusisto KM, Bebel A, Vihinen M, Schleutker J, Sallinen SL
- Issue date: 2011 Feb 28