Germline RECQL mutations are associated with breast cancer susceptibility

Nat Genet. 2015 Jun;47(6):643-6. doi: 10.1038/ng.3284. Epub 2015 Apr 27.


Several moderate- and high-risk breast cancer susceptibility genes have been discovered, but more are likely to exist. To discover new breast cancer susceptibility genes, we used 2 populations (from Poland and Quebec, Canada) and applied whole-exome sequencing in a discovery phase (n = 195), followed by validation. We identified rare recurrent RECQL mutations in each population. In Quebec, 7 of 1,013 higher-risk breast cancer cases and 1 of 7,136 newborns carried the c.634C>T (p.Arg215*) variant (P = 0.00004). In Poland, 30 of 13,136 unselected breast cancer cases and 2 of 4,702 controls carried the c.1667_1667+3delAGTA (p.K555delinsMYKLIHYSFR) variant (P = 0.008). RECQL is implicated in resolving stalled DNA replication forks to prevent double-stranded DNA (dsDNA) breaks. This function is related to that of other known breast cancer susceptibility genes, many of which are involved in repairing dsDNA breaks. We conclude that RECQL is a breast cancer susceptibility gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Molecular Sequence Data
  • Pedigree
  • RecQ Helicases / genetics*


  • RECQL protein, human
  • RecQ Helicases