Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

Breast Cancer Res Treat. 2012 Apr;132(2):421-8. doi: 10.1007/s10549-011-1596-x. Epub 2011 May 26.

Abstract

Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort (P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers (BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Analysis of Variance
  • Asian People / genetics*
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Chi-Square Distribution
  • China / epidemiology
  • DNA Mutational Analysis
  • Exons
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Heredity
  • Humans
  • Immunohistochemistry
  • Introns
  • Middle Aged
  • Pedigree
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2