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 including status of deficiencies of mismatch repair (dMMR), mutation of PIK3CA, BRAF and KRAS 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 at the Sixth Affiliated Hospital of Sun Yat-sen University. 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, including 947 EOCRC patients and 3521 LOCRC patients, were analyzed in this study. Compared with LOCRC patients, EOCRC patients were more likely to have status of dMMR (odds ratio [OR], 2.52; 95% confidence interval [CI], 2.05-3.10; P<0.001), regardless of tumor location, so were loss of MSH2 and MSH6 (OR, 4.31; 95% CI, 2.86-6.48; P<0.001; OR, 3.40; 95% CI, 2.42-4.76; P<0.001, respectively). Loss of MLH1 and PMS2 were detected more frequently in EOCRC overall (OR, 2.11; 95% CI, 1.55-2.87; P<0.001; OR, 1.83; 95% CI, 1.42-2.35; P<0.001, respectively), but only in left-side and right-side colon rather than in rectum. EOCRC patients were more likely to be detected with mutation of PIK3CA (OR, 1.24; 95% CI, 1.01-1.53; P=0.041), which only trended to exist in the left-side colon (OR, 1.51; CI, 0.98-2.33; 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; CI, 1.02-1.77; P=0.04) among EOCRC patients.
Conclusions
Status of dMMR, mutation of PIK3CA, BRAF and KRAS were 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.