Breast cancer predisposing alleles in Poland

Breast Cancer Res Treat. 2005 Jul;92(1):19-24. doi: 10.1007/s10549-005-1409-1.

Abstract

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Cell Cycle Proteins / genetics*
  • Checkpoint Kinase 2
  • Female
  • Genes, BRCA1*
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Poland / epidemiology
  • Prevalence
  • Protein Serine-Threonine Kinases / genetics*
  • Risk
  • Risk Assessment

Substances

  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases