BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma

Int J Gynecol Cancer. 2010 Oct;20(7):1148-53. doi: 10.1111/IGC.0b013e3181ef622d.

Abstract

Introduction: Whether and to what extent germline mutations in the BRCA1 and BRCA2 genes increase the risk for developing uterine serous carcinoma (USC) remain controversial. We assessed the rate of the 3 predominant BRCA1/2 mutations in Jewish patients with USC and the relevance of carrier status to clinicopathological features and survival.

Methods: Jewish patients with histologically confirmed USC diagnosed between April 1997 and December 2007 were genotyped for the 3 predominant BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method and log-rank tests were used for survival analyses.

Results: Overall, 8 (25.8%) of 31 Jewish patients with USC who participated in the study were mutation carriers: 4 were BRCA2 (6174delT) carriers and 2 each carried the BRCA1 mutations (185delAG and 5382insC). The median ages of the carriers and the noncarriers were 66 and 74 years, respectively (P = 0.124). Four (50%) of the mutation carriers and 2 (8%) of the noncarriers had a family history of breast-ovarian cancer (P = 0.026). With a median follow-up of 76 months, the overall median survival time was 25 months. No significant differences in the median survival time, 2-year survival, or progression-free survival were noted between the mutation carriers and the noncarriers.

Conclusions: The high rate of the predominant BRCA1/2 mutations in unselected Jewish USC patients, if confirmed by future studies, suggests that USC could be considered an expression of the hereditary breast-ovarian cancer syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics
  • Chemotherapy, Adjuvant
  • Cystadenocarcinoma, Serous / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics*
  • Humans
  • Jews / genetics*
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Uterine Neoplasms / genetics*

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human