BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families

Br J Cancer. 2004 Mar 22;90(6):1244-51. doi: 10.1038/sj.bjc.6601656.


Worldwide variation in the distribution of BRCA1 and BRCA2 mutations is well recognised, and for the Belgian population no comprehensive studies about BRCA1/2 mutation spectra or frequencies have been published. We screened the complete coding region of both genes in 451 individuals from 349 Belgian families referred to a family cancer clinic and identified 49 families with a BRCA1 and 26 families with a BRCA2 mutation. Six major recurrent mutations (BRCA1 IVS5+3A>G, 2478-2479insG, E1221X and BRCA2 IVS6+1G>A, 6503-6504delTT, 9132delC) accounted for nearly 60% of all mutations identified. Besides 75 true pathogenic mutations, we identified several variants of unknown clinical significance. In combination with a family history, an early average age of female breast cancer diagnosis (P<0.001), and the presence of a relative with ovarian cancer (P<0.0001) or multiple primary breast cancers (P=0.002), increased the chance for finding a mutation. Male breast cancer was indicative of a BRCA2 mutation segregating in the family (P=0.002). Mutations in the 5'-end of BRCA1 and BRCA2 were associated with a significantly increased risk for ovarian cancer relative to the central portion of the gene. Our study suggests a role for additional breast cancer susceptibility genes in the Belgian population, since mutation detection ratios were low in high-risk breast cancer-only families as compared to breast-ovarian cancer families. Given the large proportion of recurring mutations, molecular testing can now be organised in a more cost-effective way. Our data allow optimisation of genetic counselling and disease prevention in Belgian breast/ovarian cancer families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Belgium
  • Breast Neoplasms / genetics*
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Testing
  • Genetics, Population*
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Risk Factors