The role of ATM in breast cancer development

Breast Cancer Res Treat. 2007 Aug;104(2):121-8. doi: 10.1007/s10549-006-9406-6. Epub 2006 Oct 24.

Abstract

Complete or partial inability to sense and repair DNA damage increases the risk of developing cancer. The ataxia telangiectasia mutated (ATM) protein kinase has a crucial role in response to DNA double-strand breaks. Hereditary mutations in the ATM gene are the cause of a rare genomic instability syndrome ataxia telangiectasia (AT) characterized, among others, by elevated cancer risk. Although clear in homozygotes, numerous studies have failed to find a link between heterozygotes and cancer. However, there is increasing evidence that ATM heterozygotes have an increased risk of developing breast cancer. First, epidemiological studies conferred an increased risk of breast cancer among AT relatives. Second, in vitro studies of heterozygous cells provide strong evidence of hyperradiosensitivity. Third, some clinical studies found an increased frequency of ATM mutations among high-risk breast cancer families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / etiology*
  • Cell Cycle Proteins / physiology*
  • DNA-Binding Proteins / physiology*
  • Humans
  • Mutation
  • Protein Serine-Threonine Kinases / physiology*
  • Tumor Suppressor Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases