A comparison study of the intratumoral microbiome in younger verses older-onset colorectal cancer (COSMO CRC).

Abstract

241 Background: Although colorectal cancer (CRC) incidence has declined overall, CRC in individuals under age 45 has risen dramatically, particularly in the distal colon and rectum (left-sided CRC). The intratumoral microbiome (MB) of young individuals may be responsible. Certain bacteria disrupt colonic luminal integrity and promote inflammation, leading to oncogenic mutations in colonic epithelial cells. Fusobacterium nucleatum ( F. nuc) promotes CRC by suppressing immune response within the tumor microenvironment, activating the β-catenin pathway, and causing chemoresistance due to autophagy. Methods: We compared the intratumoral MB in CRC patients (pts) diagnosed before age 45 and after age 65. Primary and metastatic tumors were included. DNA was extracted from tumors and analyzed using 16S ribosomal gene sequencing. We compared the frequency of F. nuc and other bacterial and fungal DNA in tumors from younger- vs. older-onset CRC pts. Results: Tumors from 18 younger pts (median age 39.2 years) and 13 older pts (median age 72.8 years) underwent analysis. In total, 478 unique bacterial and fungal species were detected. F. nuc was found in tumors of 5 younger pts (28%, 4 left-sided and 1 right-sided primary) and 3 older pts (23%, 1 left-sided and 2 right-sided; P = NS, Fisher’s Exact test). A significant difference was seen in the rate of Moraxella osloensis (11% vs. 46%, P = 0.043, Fisher’s Exact test) in younger vs. older pts. There was no significant difference in MB diversity in younger vs. older pts. Conclusions: F. nuc is present in a greater number of tumors in pts with CRC diagnosed before age 45 than previously thought. Intratumoral bacterial profiling may discover patterns that explain the rising incidence of CRC in younger individuals and might eventually inform the development of novel therapeutics and adaptive cancer screening methods.