Furthermore, genomic profiles of early-onset CRC tumors varied by race and ethnicity.
Notably, non-Hispanic Black patients with early-onset CRC had a 4-fold higher frequency of mutations in CREBBP and TGFBR2, compared with non-Hispanic Black patients who had late-onset CRC. This pattern was unique to the population of non-Hispanic Black patients.
Non-Hispanic Black patients also had a higher tumor mutation burden than non-Hispanic White patients, which was seen in both early- and late-onset CRC.
Among Asian/Pacific Islander patients, when compared with late-onset CRC, early-onset CRC was characterized by a lower frequency of mutations in PIK3CA and a higher frequency of mutations in APC and FAT-1. Mutations in these genes were not associated with an increased risk of early-onset CRC in non-Hispanic White patients and did not persist in the overall model.
Non-Hispanic White patients with early-onset CRC had a greater frequency of mutations in TP53 and SMAD2 but a lower frequency of mutations in FLT4, when compared with non-Hispanic White patients who had late-onset CRC.
Unique LRP1B, TGFBR2, APC, and PIK3CA mutation frequencies were observed in early-onset CRC patients with microsatellite-stable tumors across all racial and ethnic groups.
As suggested by Dr Holowatyj, investigations into the mechanisms responsible for these distinct genomic patterns in early-onset CRC are needed.
Value of Global Biobanks and Registries
The GENIE registry does not provide potentially relevant information about cancer stage, tumor grade, survival, or personal risk factors like obesity, alcohol use, or smoking exposure.
Nonetheless, as the incidence of CRC varies widely by region, global efforts like the GENIE registry may be vital to uncovering heterogeneity in tumor biology and potential explanations for observed differences in treatment response and clinical outcome.
Data from global tissue banks and information exchange projects like GENIE provide the statistical power to inform trial design and translational research. This is particularly important for rare cancers and rare variants of common malignancies.
Projects like GENIE exemplify how international collaboration is critically important for investigating these complex, clinically relevant issues and how acquiring biospecimens for shared tissue banks is an investment in cancer care that can pay dividends in addressing issues that vex oncologists throughout the world.
Disclosures: Dr Holowatyj disclosed funding from the National Institutes of Health, the Dalton Family Foundation, and the American Cancer Society.
1. Holowatyj AN. Society meets biology: Racial/ethnic disparities in early-onset colorectal cancers. Presented at AACR Colorectal Cancer 2021. October 21-22, 2021.
2. Siegel RL, Miller KD, Sauer AG, et al. Colorectal Cancer Statistics, 2020. CA Cancer J Clin. 2020;70:145-164. https://doi.org/10.3322/caac.21601
3. Willauer AN, Liu Y, Pereira AAL, et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer. 2019;125(12):2002–2010. doi:10.1002/cncr.31994
4. Holowatyj AN, Gigic B, Herpel E, et al. Distinct molecular phenotype of sporadic colorectal cancers among young patients based on multiomics analysis. Gastroenterology. 2020;158(4):1155-1158.e2. doi:10.1053/j.gastro.2019.11.012
5. Theuer CP, Wagner JL, Taylor TH, et al. Racial and ethnic colorectal cancer patterns affect the cost-effectiveness of colorectal cancer screening in the United States. Gastroenterology. 2001;120(4):848-56. doi:10.1053/gast.2001.22535
6. Holowatyj AN, Ruterbusch JJ, Rozek LS, Cote ML, Stoffel EM. Racial/ethnic disparities in survival among patients with young-onset colorectal cancer. J Clin Oncol. 2016;34(18):2148-56. doi:10.1200/JCO.2015.65.0994