Discovering moderate-risk breast cancer susceptibility genes

Curr Opin Genet Dev. 2010 Jun;20(3):268-76. doi: 10.1016/j.gde.2010.02.009. Epub 2010 Mar 24.


To date, five moderate-risk breast cancer susceptibility genes have been convincingly identified: CHEK2, ATM, BRIP1, PALB2, and NBS1. Moderate-risk breast cancer alleles confer increased breast cancer risks of two to fourfold compared to the 10% risk in the general population. In contrast to the high-risk BRCA1 and BRCA2 genes, moderate-risk genes typically have a limited number of variants that confer breast cancer risks. The prevalence of the variants usually varies widely among different geographical or ethnic populations, ranging from essentially absent up to 1.5% (i.e. 'rare' variants). Since moderate-risk breast cancer alleles are clinically not recognizable when inherited as single mutant, one usually encounters them in a polygenic setting and consequently in incomplete cosegregation with the breast cancer phenotype. As a result, discovery of moderate-risk breast cancer genes requires conclusive statistical evidence from association studies of hundreds of breast cancer cases and population-matched controls.

Publication types

  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics*
  • Cell Cycle Proteins / genetics
  • Checkpoint Kinase 2
  • DNA-Binding Proteins / genetics
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Nuclear Proteins / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • RNA Helicases / genetics
  • Risk Factors
  • Tumor Suppressor Proteins / genetics


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fanconi Anemia Complementation Group N Protein
  • Fanconi Anemia Complementation Group Proteins
  • NBN protein, human
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases
  • BRIP1 protein, human
  • RNA Helicases