Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer

Cancer Sci. 2008 Oct;99(10):1967-76. doi: 10.1111/j.1349-7006.2008.00944.x.


The prevalence of BRCA1/2 germline mutations in Japanese patients suspected to have hereditary breast/ovarian cancer was examined by a multi-institutional study, aiming at the clinical application of total sequencing analysis and validation of assay sensitivity in Japanese people using a cross-sectional approach based on genetic factors estimated from personal and family histories. One hundred and thirty-five subjects were referred to the genetic counseling clinics and enrolled in the study. Full sequencing analysis of the BRCA1/2 gene showed 28 types of deleterious mutations in 36 subjects (26.7%), including 13 types of BRCA1 mutations in 17 subjects (12.6%) and 15 types of BRCA2 mutations in 19 subjects (14.1%). Subjects were classified into five groups and 22 subgroups according to their personal and family history of breast and/or ovarian cancer, and the prevalence of deleterious mutations was compared with previously reported data in non-Ashkenazi individuals. Statistical analysis using the Mantel-Haenszel test for groups I through IV revealed that the prevalence of Japanese subjects was significantly higher than that of non-Ashkenazi individuals (P = 0.005, odds ratio 1.87, 95% confidence interval 1.22-2.88). Family history of the probands suffering from breast cancer indicated risk factors for the presence of deleterious mutations of BRCA1/2 as follows: (1) families with breast cancer before age 40 within second degree relatives (P = 0.0265, odds ratio 2.833, 95% confidence interval 1.165-7.136) and (2) families with bilateral breast cancer and/or ovarian cancer within second degree relatives (P = 0.0151, odds ratio 2.88, 95% confidence interval 1.25-6.64).

MeSH terms

  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Confidence Intervals
  • Cross-Sectional Studies
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Incidence
  • Japan / epidemiology
  • Odds Ratio
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics*
  • Prevalence
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Sequence Analysis, DNA