Estimating the number of potential family members eligible for BRCA1 and BRCA2 mutation testing in a "Traceback" approach

Genet Epidemiol. 2018 Feb;42(1):117-122. doi: 10.1002/gepi.22095. Epub 2017 Nov 30.

Abstract

U.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high-grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain unidentified and at risk. Accordingly, an approach termed "Traceback" has been proposed in which probands are retrospectively identified by testing archived pathology specimens, and family members are traced to provide genetic counseling and testing. We used population-based data to estimate the number of family members who might be contacted through such a program. We used incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the number of women diagnosed with HGOC from 2005 to 2016, and census data to estimate the number of spouses, offspring, and siblings (both sexes). Using overall survival for HGOC from SEER and all-cause mortality rates from the Centers for Diseases Control and Prevention, we estimated the number of patients, spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high mortality rate of HGOC, consent from living probands may be possible in only 42% of the cases; consent to test pathology specimens would need to be sought from next of kin for the remainder. In 2017, an estimated 406,919 living next of kin (spouses, siblings, offspring) would be available for potential consent. Testing archived ovarian cancer pathology specimens may enable the identification of BRCA1/2 mutation carriers, but consent from next of kin would be required in in 58% of cases. Although Traceback offers the possibility of identifying unaffected BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of methods to secure consent are needed.

Keywords: BRCA1 and BRCA2; genetic risk assessment; ovarian cancer.

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Cause of Death
  • DNA Mutational Analysis*
  • Family* / psychology
  • Female
  • Genes, BRCA1
  • Genetic Counseling
  • Genetic Testing / methods*
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics
  • Heterozygote*
  • Humans
  • Incidence
  • Informed Consent / psychology
  • Male
  • Mutation*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Survival Analysis

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human