Clinicopathological and molecular characteristics of early-onset vs late-onset colorectal cancer according to tumor location

Abstract

Background: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing worldwide in decade when screening of colorectal cancer (CRC) is more prevalent. The clinicopathological and molecular characteristics of EOCRC have not yet been clarified. This study aims to evaluate clinicopathological and molecular features among EOCRC and late-onset colorectal cancer (LOCRC) patients according to different tumor locations.

Methods: We identified CRC patients from a prospectively maintained CRC database between January 2015 and December 2018. The clinicopathological and molecular characteristics including dMMR, mutation of PIK3CA, BRAF and KRAS were compared between EOCRC and LOCRC. The relationships according to different tumor locations were assessed.

Results: Totally 4468 patients were analyzed in this study. Compared to LOCRC patients, EOCRC patients were more likely to have status of dMMR (OR, 2.52; P < 0.001), regardless of tumor location. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; P = 0.041), which only tended to exist in the left-side colon (OR, 1.51; P = 0.06), but not in the right-side colon or rectum. No significant difference was found for BRAF or KRAS mutation, but mutation of KRAS was more frequently found in left-side colon (OR, 1.34; P = 0.04) among EOCRC patients.

Conclusion: Status of dMMR, mutation of PIK3CA, BRAF and KRAS was different between EOCRC and LOCRC patients according to different tumor locations, which implied that EOCRC might be a unique subgroup of CRC patients. Further investigations of molecular and genetic differences should be performed to help define new diagnosing and therapeutical strategies for EOCRC patients.

Keywords: Early-onset colorectal cancer; Mismatch repair deficiency; Molecular characteristics; Tumor location.