Primary care providers' responses to unsolicited Lynch syndrome secondary findings of varying clinical significance

Genet Med. 2021 Oct;23(10):1977-1983. doi: 10.1038/s41436-021-01225-7. Epub 2021 Jun 10.


Purpose: How primary care providers (PCPs) respond to genomic secondary findings (SFs) of varying clinical significance (pathogenic, uncertain significance [VUS], or benign) is unknown.

Methods: We randomized 148 American Academy of Family Physicians members to review three reports with varying significance for Lynch syndrome. Participants provided open-ended responses about the follow-up they would address and organized the SF reports and five other topics in the order they would prioritize responding to them (1 = highest priority, 6 = lowest priority).

Results: PCPs suggested referrals more often for pathogenic variants or VUS than benign variants (72% vs. 16%, p < 0.001). PCPs were also more likely to address further workup, like a colonoscopy or esophagogastroduodenoscopy, in response to pathogenic variants or VUS than benign variants (43% vs. 4%, p < 0.001). The likelihoods of addressing referrals or further workup were similar when PCPs reviewed pathogenic variants and VUS (both p > 0.46). SF reports were prioritized highest for pathogenic variants (2.7 for pathogenic variants, 3.6 for VUS, 4.3 for benign variants, all p ≤ 0.014).

Conclusion: Results suggest that while PCPs appreciated the differences in clinical significance, disclosure of VUS as SFs would substantially increase downstream health-care utilization.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Genomics
  • Humans
  • Primary Health Care
  • United States