Comparison of selection strategies for genetic testing of patients with hereditary nonpolyposis colorectal carcinoma: effectiveness and cost-effectiveness

Cancer. 2002 Nov 1;95(9):1848-56. doi: 10.1002/cncr.10910.


Background: Molecular testing for hereditary nonpolyposis colorectal carcinoma (HNPCC) is becoming standard care and it is cost-effective compared with no genetic testing. However, the best strategy for detection of HNPCC gene carriers is unknown.

Methods: We use a decision analytic model to evaluate the effectiveness and incremental cost-effectiveness of four commonly used testing strategies to detect HNPCC gene carriers. The model starts with a population of colorectal carcinoma (CRC) patients and measures costs, the number of gene carriers detected, and incremental costs per gene carrier detected.

Results: We found that germline testing on only those CRC probands who meet the Amsterdam criteria detects the fewest gene carriers and has the lowest cost whereas tumor microsatellite instability (MSI) testing of all CRC patients and families has the highest cost and detects the most gene carriers. When cost-effectiveness is considered, the mixed strategy (MSH2 and MLH1 testing on those who meet the Amsterdam criteria and germline testing for the remainder who meet less stringent modified criteria and are MSI-High) seems superior. The mixed strategy detects 59.6 mutation carriers per 1000 CRC cases and costs much less than the test all strategy, which has an incremental cost-effectiveness of $51,151. The mixed strategy often other strategies and when compared to the Amsterdam strategy, has a cost-effectiveness of only $6441 per gene carrier detected.

Conclusions: It is not very effective to limit genetic testing to only individuals who meet the Amsterdam criteria, as many gene carriers are missed. However, testing all CRC patients for tumor MSI-H, although effective, may be prohibitively expensive. A mixed strategy is the more cost-effective approach.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Pair Mismatch
  • Carrier Proteins
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / economics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Cost-Benefit Analysis
  • Costs and Cost Analysis
  • DNA Repair / genetics
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins*
  • Decision Support Techniques
  • Genetic Carrier Screening
  • Genetic Testing* / economics
  • Genetic Testing* / methods
  • Germ-Line Mutation
  • Humans
  • Microsatellite Repeats / genetics
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Proto-Oncogene Proteins / genetics


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein