Success of referral to genetic counseling after positive lynch syndrome screening test

Int J Colorectal Dis. 2017 Sep;32(9):1345-1348. doi: 10.1007/s00384-017-2849-x. Epub 2017 Jun 29.

Abstract

Purpose: Lynch syndrome (LS) is a hereditary condition that increases one's risk of developing colorectal, endometrial, and other extracolonic cancers. MD Anderson Cancer Center at Cooper implemented a reflex screening protocol for DNA mismatch repair (dMMR) deficiency. Those with findings suspicious for LS were referred for genetic counseling (GC). Our goal was to assess compliance with GC and factors associated with successful follow-up.

Methods: Immunohistochemistry (IHC) for the MMR proteins MSH2, MLH1, MSH6, and PMS2 was performed on all colorectal tumor resections from patients ≤70 years old and all stage II cancers. Tumors with loss of MLH1/PMS2 were subsequently tested for BRAF mutation or MLH1 promoter methylation to identify tumors with likely epigenetic inactivation of MLH1. Patients with loss of MLH1/PMS2 without BRAF mutations or with absence of MLH1 promoter methylation and those with loss of MSH2/MSH6 were referred to GC. Compliance with GC was assessed.

Results: Between March 2014 and August 2016, 203 tumors were tested by IHC. Fifteen (7.4%) patients had abnormal MMR protein expression patterns in the absence of BRAF mutation or MLH1 promoter methylation suggestive of possible LS. GC compliance was 35.7% overall and 85.7% in those with family history of LS-associated cancers.

Conclusions: Overall, GC compliance was relatively low in our study. Interestingly, patients with a strong family history of LS-associated neoplasms were more likely to pursue GC. In the future, assessing and addressing barriers to seeking GC will provide opportunities to improve patient care through increased identification of patients with cancer predisposition syndromes.

Keywords: Genetic counseling compliance; HNPCC; Lynch syndrome; Screening.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / chemistry
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / therapy
  • DNA Methylation
  • DNA Mutational Analysis
  • Epigenesis, Genetic
  • Female
  • Genetic Counseling*
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Heredity
  • Humans
  • Immunohistochemistry
  • Male
  • Mutation
  • Patient Compliance*
  • Pedigree
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Referral and Consultation*
  • Retrospective Studies
  • Texas

Substances

  • Biomarkers, Tumor