ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry

PLoS One. 2016 Jun 7;11(6):e0156820. doi: 10.1371/journal.pone.0156820. eCollection 2016.


Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer.

MeSH terms

  • Age of Onset
  • Breast Neoplasms / genetics*
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • MCF-7 Cells
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Quebec


  • ABRAXAS1 protein, human
  • Carrier Proteins

Supplementary concepts

  • Breast Cancer, Familial