Somatic Mutation Profiles of Colorectal Cancer by Birth Cohort

Area of Science:

• Oncology
• Genomics
• Cancer Epidemiology

Background:

• Colorectal cancer (CRC) incidence is increasing globally, particularly among individuals born after 1960.
• The underlying reasons for this trend, especially potential changes in tumor genomics across birth cohorts, remain unclear.

Purpose of the Study:

• To investigate whether the somatic mutation profiles of colorectal tumors differ between birth cohorts.
• To determine if genomic alterations in CRC are associated with generational shifts in disease incidence.

Main Methods:

• Retrospective analysis of somatic next-generation sequencing data from 369 colorectal tumors.
• Assessment of microsatellite instability (MSI) status and gene pathway mutations.
• Statistical analysis using logistic regression, adjusting for CRC stage, location, treatment, and age.

Main Results:

• No statistically significant differences were found in mutation prevalence or pathway-level alterations in colorectal cancer by birth cohort.
• While microsatellite instability-high (MSI-H) tumors were initially associated with earlier birth years, this finding was not significant after adjusting for confounders.
• Tumor mutational burden did not correlate with birth year after controlling for relevant factors.

Conclusions:

• The mutational landscape of colorectal cancer does not appear to vary significantly across birth cohorts.
• Observed increases in CRC incidence among younger generations are unlikely to be driven by changes in tumor genomics.
• Larger studies are warranted to confirm these findings regarding colorectal cancer genomics and generational trends.