title: Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy.
abstract: Breast cancer (BC) in men is rare compared with BC in women, but its incidence is increasing along with attention toward this uncommon disease. Although with some differences, male and female BC share similar genetic predisposition factors, including BRCA1/2, CHEK2, and PALB2 mutations. As other BRCA1/2 functionally related DNA repair genes, such as CHEK2 and PALB2, BRIP1 is considered a moderate-penetrance BC susceptibility gene. At present, the role of BRIP1 on BC susceptibility in men is unknown. In this study, we aimed to assess whether BRIP1 variants may contribute to male BC (MBC) risk, by screening 97 MBC cases, all negative for BRCA1/2, CHEK2, and PALB2 mutations, selected from a population-based series of 126 MBCs from Central Italy. A total of five BRIP1 germ-line sequence alterations, three coding, and two non-coding variants, were detected in our series. The two non-coding variants IVS4-28G > A and 3'UTR 4049C > T were classified as neutral by in silico analysis. Of the three coding variants, one was a silent variant (E879E) and two resulted in amino acid substitution (R264W and P919S) showing a putative pathogenic role by in silico analysis. However, further analysis of tumor-associated loss of heterozygosity and the frequency of variant alleles, tested in 203 male population controls, suggested a neutral effect for both of these variants. Overall, our results indicate that BRIP1 variants may not play a relevant role in MBC predisposition.
authors.affiliation: Department of Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, Rome, 00161, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Silvestri
authors.forename: Piera
authors.initials: P
authors.lastname: Rizzolo
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D051856:Fanconi Anemia Complementation Group Proteins; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D007558:Italy / Q000453:epidemiology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020365:RNA Helicases / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases