EP707 - Somatic tumor mutation testing in early-onset colorectal cancer patients: a single center retrospective analysis

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Purpose/Background: Early-onset colorectal cancer (EOCRC), defined as patients diagnosed with CRC at age 50 years old or younger, has steadily increased in incidence over the past 20 years, with EOCRC now accounting for approximately 10% of all new diagnoses of CRC. Studies have found that, compared to later-onset CRC, a higher proportion of EOCRC patients are black with a worse median overall survival compared to white patients. Recent studies have highlighted that racial disparities in later-onset CRC are primarily driven by socioeconomic factors, while the disparities observed in EOCRC persist independent of socioeconomic factors. Thus, we hypothesized that there is a unique biology to tumors in EOCRC that disproportionally affects black patients may be identifiable through analysis of somatic tumor mutation data.

Methods/Interventions: We performed a retrospective review of patients with a new diagnosis of CRC between 2015 and 2022 who were treated at a large tertiary care center. Review of the electronic health records included patient demographics, clinical and pathologic tumor characteristics and treatment outcomes. The primary outcome was identification of somatic tumor mutations in EOCRC. Patient and tumor characteristics associated with increased rate of somatic mutations were identified by bivariate analysis.

Results/Outcomes: We identified 390 patients with a new diagnosis of CRC, 99 (25%) of which met criteria for EOCRC; with 61 (61.6%) white, 32 (32.3%) black, and 6 (0.06%) other. Of the 99 patients with EOCRC, 46 (46.5%) had somatic mutation analysis performed. A similar rate of testing was observed for white (30/61) and black (16/32) patients. Of the individuals tested, 41 (46%) were identified to have a somatic mutation in at least one gene. We found a significant difference in mutation frequency between white and black patients in KRAS (0.3 vs 0.69; p= 0.012) and all RAS combined (0.33 vs 0.81; p= 0.002). Rates of APC mutations were 0.27 and 0.44 in white and black patients, respectively (p = 0.239). Rates of SMAD4 mutations were 0.07 and 0.19 in white and black patients, respectively (p = 0.240). Rates of TP53 mutations were similar between white and black patients (0.23 vs 0.19, respectively; p = 0.720).

Conclusion/Discussion: This study highlights key differences in tumor biology between white and black patients with EOCRC at a single center academic hospital in South Carolina, with higher rates of KRAS mutations observed in black patients compared to white patients. This is of particular interest for patients with CRC as KRAS mutation status plays an important role in determining disease prognosis and informs treatment decisions. Our findings highlight a possible need for increased rates of somatic tumor mutation testing in black patients with EOCRC. Further studies should be conducted to determine the generalizability of these findings to other academic centers and to correlate mutation status in this population with disease outcomes.