Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy

作者：Silvestri Valentina; Rizzolo Piera; Falchetti Mario; Zanna Ines; Masala Giovanna; Bianchi Simonetta; Palli Domenico; Ottini Laura^*

来源：Breast Cancer Research and Treatment, 2011, 126(2): 539-543.

DOI：10.1007/s10549-010-1289-x

• BRCA1
• BRCA2
• BRIP1
• CHEK2
• Germ-line mutations
• Male Breast Cancer
• PALB2

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.

• 出版日期2011-4