Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis

Ann Intern Med. 2023 May;176(5):585-595. doi: 10.7326/M22-0846. Epub 2023 May 9.


Background: The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.

Objective: To estimate the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH).

Design: Decision analytic Markov model.

Data sources: Published literature.

Target population: Separate age-based cohorts (ages 20 to 60 years at time of screening) of racially and ethnically representative U.S. adults.

Time horizon: Lifetime.

Perspective: U.S. health care payer.

Intervention: Population genomic screening using clinical sequencing with a restricted panel of high-evidence genes, cascade testing of first-degree relatives, and recommended preventive interventions for identified probands.

Outcome measures: Incident breast, ovarian, and colorectal cancer cases; incident cardiovascular events; quality-adjusted survival; and costs.

Results of base-case analysis: Screening 100 000 unselected 30-year-olds resulted in 101 (95% uncertainty interval [UI], 77 to 127) fewer overall cancer cases and 15 (95% UI, 4 to 28) fewer cardiovascular events and an increase of 495 quality-adjusted life-years (QALYs) (95% UI, 401 to 757) at an incremental cost of $33.9 million (95% UI, $27.0 million to $41.1 million). The incremental cost-effectiveness ratio was $68 600 per QALY gained (95% UI, $41 800 to $88 900).

Results of sensitivity analysis: Screening 30-, 40-, and 50-year-old cohorts was cost-effective in 99%, 88%, and 19% of probabilistic simulations, respectively, at a $100 000-per-QALY threshold. The test costs at which screening 30-, 40-, and 50-year-olds reached the $100 000-per-QALY threshold were $413, $290, and $166, respectively. Variant prevalence and adherence to preventive interventions were also highly influential parameters.

Limitations: Population averages for model inputs, which were derived predominantly from European populations, vary across ancestries and health care environments.

Conclusion: Population genomic screening with a restricted panel of high-evidence genes associated with 3 CDC Tier 1 conditions is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.

Primary funding source: National Human Genome Research Institute.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cardiovascular Diseases*
  • Cost-Benefit Analysis
  • Cost-Effectiveness Analysis
  • Humans
  • Hyperlipoproteinemia Type II*
  • Mass Screening
  • Metagenomics
  • Middle Aged
  • Quality-Adjusted Life Years
  • Young Adult