May 29, 2018
2 min read

Colorectal cancer in younger patients develops via different genetic pathway

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Matthew Kalady
Matthew Kalady

Patients aged younger than 50 years who develop colorectal cancer were less likely to do so through the serrated polyp pathway, which is more common in older patients, according to research presented at the American Society of Colorectal Surgeons Annual Scientific Meeting in Nashville.

Matthew Kalady, MD, co-director of Cleveland Clinic’s comprehensive colorectal cancer program, and colleagues said this difference in biology explains the left predominant cancer distribution in younger patients and should focus efforts to understand and prevent cancer on causes of chromosomal instability.

“Colorectal cancers are diverse and can form through a number of different genetic and molecular pathways,” Kalady told Healio Gastroenterology and Liver Disease. “The fact that these young cancers tend to be on the left side of the colon and rectum, and that they seem to arise from a particular genetic pathway and not the methylation pathway, will allow researchers to focus on these particular mechanisms to try to figure underlying reasons.”

Kalady and colleagues compared tumor biology in patients aged younger than 50 (n = 57; 11.5%) with patients older than 50 (n = 440; 88.5%). They reviewed resected CRC from a tumor bank and checked each sample for CpG island methylator phenotype (CIMP) status, as well as KRAS and BRAF mutations.

Researchers observed 497 cancers, 57 (11.5%) of which were from patients aged younger than 50 years. None of these cancers in the younger group were hypermethylated compared with 97 (22%) of the cancers from patients aged older than 50 years (P < .001). There was also an increase in the proportion of CIMP-high cancers with each decade of age at diagnosis.

Although none of the younger patients had BRAF mutation, 47 of the older patients did (10.6%; P < .001). Additionally, KRAS mutation was less common in younger patients compared with older patients (22.8% vs. 30.7%; P < .01).

Kalady and colleagues found that tumors in younger patients were less likely to be centrally located compared with the older group (19.3% vs. 51.8%; P < .001).

“Recent work by our group has demonstrated a high prevalence of left sided and rectal cancers in younger patients, which suggests that people in their 40s might benefit from screening endoscopy that can reach these areas, such as flexible proctosigmoidoscopy,” Kalady said. – by Alex Young


Chouhan H, et al. Abstract S61. American Society of Colorectal Surgeons Annual Scientific Meeting; May 19-23; Nashville, Tenn.

Disclosures: Kalady reports no relevant financial disclosures. Healio Gastroenterology and Liver Disease was unable to determine the other authors relevant financial disclosures at the time of publication.