Associations with other cancer-related biomarkers might contribute to poor outcomes in RAS-altered, younger patients with colorectal cancer

TL;DR

Younger patients with RAS-altered colorectal cancer have worse outcomes, possibly due to differences in biomarker associations.

Contribution

The study identifies age-related differences in biomarker associations in RAS-altered colorectal cancer patients.

Findings

Younger patients with RAS-altered tumors are more likely to be MSI-high.

RNF43 mutations are more common in younger RAS-altered CRC patients.

APC wild-type status is more frequent in younger RAS-altered CRC patients.

Abstract

Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS-altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.0%) of whom were ≤50 years old, and 454 (49.1%) who had RAS-altered tumors. For 3 biomarkers, RNF43, APC, and microsatellite instability (MSI), the association with RAS status was significantly modified by age after adjustment for multiple testing. Specifically, younger patients with RAS-altered tumors were more likely to be MSI-high, RNF43 mutated, and APC wild type. These differences might contribute to the observed pattern of diminished survival in younger versus older patients with CRC with RAS-mutated tumors undergoing liver metastasis resection.

In patients undergoing liver resection with RAS-altered colorectal cancers (CRCs), there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, this study evaluated differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC.