Association of PALB2 sequence variants with the risk of early-onset breast cancer in patients from Turkey

Mol Biol Rep. 2016 Nov;43(11):1273-1284. doi: 10.1007/s11033-016-4061-4. Epub 2016 Aug 29.

Abstract

The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA)and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.

Keywords: Early-onset breast cancer; Moderate-penetrance genes; PALB2 gene; Turkish population.

MeSH terms

  • Adult
  • Age of Onset
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis / methods
  • Fanconi Anemia Complementation Group N Protein
  • Female
  • Genetic Association Studies / methods*
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA / methods
  • Tumor Suppressor Proteins / genetics*
  • Turkey
  • White People / genetics*
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Fanconi Anemia Complementation Group N Protein
  • Nuclear Proteins
  • PALB2 protein, human
  • Tumor Suppressor Proteins