Abstract

Many hereditary gastrointestinal cancer predisposition syndromes (HGCPS), including Lynch syndrome (LS), increase the risk for colorectal cancer (CRC). Sporadic CRC in average-risk individuals has shifted toward younger ages; however, the same trend in patients with HGCPS/LS remains underexplored. We aimed to evaluate temporal trends in age at CRC diagnosis among patients with HGCPS/LS compared with a non-hereditary/average risk cohort in a large national database.

We used the TriNetX database to identify patients with HGCPS/LS from 2010 to 2024. We compared age at CRC diagnosis between patients with HGCPS/LS and a non-hereditary/average risk cohort.

Among 136,394 patients with HGCPS/LS, 6,561 (4.8%) were diagnosed with CRC, compared with 364,189 (0.34%) in the average risk cohort. The peak age at CRC diagnosis shifted earlier by 10 years, from 45-54 years in 2010-2017 to 35-44 years in 2018-2024, and the proportion diagnosed before age 45 rose from 35% to 51%. Among HGCPS/LS patients, the mean age at CRC diagnosis declined from 51±17 to 47±18 years; during 2018-2024 it was 47±18 years <i>vs.</i> 58±14 years in the average risk cohort. Overall, 55.4% of HGCPS/LS cases occurred by age 49 <i>vs.</i> 13.8% of controls, and HGCPS/LS patients were diagnosed at a median age 20.0 years younger (P<0.001). They were also more often female (56% <i>vs.</i> 46%), obese (31% <i>vs.</i> 22%), and tobacco users (18% <i>vs.</i> 15%; all P<0.01).

CRC is increasingly diagnosed at younger ages among patients with HGCPS/LS, paralleling trends in the average-risk population and likely reflecting combined environmental, lifestyle, and genetic-testing influences. These findings support continued individualized, gene- and family history-based surveillance rather than uniform age thresholds.

EDRN PI Authors

• Bresalier, Bob

Medline Author List

• Burke C
• Eldesouki MH
• Ibrahim A
• Katona BW
• Shaukat A

PubMed ID

Sources

• Cancer Data Expo

Appears In

J Gastrointest Oncol, 2026 Jun (issue 3)