A possible role of FANCM mutations in male breast cancer susceptibility: Results from a multicenter study in Italy

V. Silvestri, P. Rizzolo, V. Zelli, V. Valentini, I. Zanna, S. Bianchi, M.G. Tibiletti, L. Varesco, A. Russo, S. Tommasi, A. Coppa, C. Capalbo, D. Calistri, A. Viel, L. Cortesi, S. Manoukian, B. Bonanni, M. Montagna, D. Palli, P. RadiceP. Peterlongo, L. Ottini

Research output: Contribution to journalArticlepeer-review


Introduction Breast cancer (BC) in men is a rare disease, whose etiology appears to be associated with genetic factors. Inherited mutations in BRCA1/2 genes account for about 10–15% of all cases. FANCM, functionally linked to BRCA1/2, has been suggested as a novel BC susceptibility gene. Our aim was to test if FANCM germline mutations could further explain male BC (MBC) susceptibility. Methods We screened the entire coding region of FANCM in 286 MBCs by a multi-gene panel analysis, and compared these data with available whole exome sequencing data from 415 men used as population controls. Moreover, we genotyped the two most frequent FANCM mutations (c.5101C>T and c.5791C>T) in 506 MBCs and 854 healthy male controls. Results Two FANCM truncating mutations, the c.1432C>T (p.Arg478Ter) and c.1972C>T (p.Arg658Ter), were identified in two MBC cases (0.7%). When specifically considering cases at increased genetic risk for BC, FANCM mutation frequency raises up to 1%. One mutation, the c.2201_2202delCT (p.Ser734Terfs), was found among controls (0.24%). Mutation frequency in cases was higher than in controls, however this difference was not statistically significant. FANCM c.5101C>T was not present in any of the cases and controls analyzed, whereas FANCM c.5791C>T was found in two controls (0.23%). Conclusion Rare FANCM truncating mutations, other than c.5101C>T and c.5791C>T, may have a role in MBC susceptibility. The inclusion of FANCM in gene panels for research purpose would allow for the identification of a higher number of mutation carriers, thus helping estimate BC risk associated with FANCM mutations. © 2017
Original languageEnglish
Pages (from-to)92-97
Number of pages6
Publication statusPublished - 2018


  • BRCA1/2
  • Breast cancer susceptibility
  • Germline mutations
  • Male breast cancer
  • arginine
  • cytosine
  • serine
  • thymine
  • DNA helicase
  • FANCM protein, human
  • tumor marker
  • adult
  • aged
  • Article
  • breast cancer
  • cancer susceptibility
  • controlled study
  • FANCM gene
  • gene frequency
  • gene function
  • genetic code
  • genetic identification
  • genetic risk
  • genetic screening
  • germline mutation
  • heterozygote
  • human
  • Italy
  • major clinical study
  • male
  • multicenter study (topic)
  • mutation rate
  • mutational analysis
  • population research
  • priority journal
  • tumor suppressor gene
  • very elderly
  • whole exome sequencing
  • breast tumor
  • case control study
  • clinical trial
  • genetic predisposition
  • genetics
  • genotype
  • middle aged
  • multicenter study
  • risk factor
  • whole genome sequencing
  • young adult
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Breast Neoplasms, Male
  • Case-Control Studies
  • DNA Helicases
  • Genetic Predisposition to Disease
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Whole Genome Sequencing
  • Young Adult


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