Germline RAP80 mutations and susceptibility to breast cancer

Mohammad Reza Akbari, Parviz Ghadirian, Andre Robidoux, Maryam Foumani, Yulong Sun, Robert Royer, Inuk Zandvakili, Henry Lynch, Steven A. Narod

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Most of the breast cancer susceptibility genes identified to date are involved in DNA repair, including BRCA1, BRCA2, PALB2, CHEK2 and BRIP1. RAP80 works upstream of BRCA1 and is essential for the localization of BRCA1 to the site of damaged DNA. To investigate whether or not RAP80 is also a breast cancer susceptibility gene, we sequenced the entire exonic regions of RAP80 in the germline DNA of 152 women with familial breast cancer, who were previously found to be negative for BRCA1 and BRCA2 mutations. No truncating mutation was identified. Eleven potentially deleterious RAP80 variants were identified; these 11 variants were genotyped in 424 more familial cases and in 726 healthy controls. Three novel p.Ala342Thr, p.Met353Thr and p.Tyr575Asp rare missense variants and a novel haplotype composed of two variants in the CpG island (c.-24149G > T and c.-24001A > G) and a variant in the 5′UTR (c.-8A > G) and a variant in the 3′UTR (c.*27A > C) were detected in 26 of 571 (4.6%) individuals with familial breast cancer, compared to 14 of 725 (1.9%) controls (P = 0.01; OR = 2.4, 95% CI = 1.2-5.1). In summary, we did not find truncating mutations of the RAP80 gene to be a cause of familial breast cancer. A novel RAP80 haplotype or rare missense mutations may be associated with a modest increased risk of breast cancer, but this observation needs to be confirmed by additional studies.

Original languageEnglish (US)
Pages (from-to)377-381
Number of pages5
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Jan 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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