QS134 - Investigating the Molecular Genetics of Early Onset Rectal Cancer by Race

Purpose/Background: The incidence of early onset colorectal cancer (EO-CRC) is rising. Many of these cancers are diagnosed at advanced stages, making studies exploring the distribution of potential therapeutic targets crucial. African Americans have a higher rate of EO-CRC with the highest rates of mortality of any ethnic group. Previous research has focused on colorectal cancer as a single entity and did not differentiate between colonic and rectal primaries. The aims of this study were to 1) investigate genomic mutational patterns in rectal cancer by age at onset ( < 50 and >50), and 2) determine if differences exist in mutational patterns by race.

Methods/Interventions: Patients diagnosed with rectal cancer from 2018-2022 were identified at a single institution. All patients who underwent surgery and had genetic testing performed were included. Early onset was defined as diagnosis prior to the age of 50. Patients under the age of 18, those with unknown race, and/or those without complete genetic profiling data (BRAF, KRAS, NRAS, PIK3CA, TP53, APC) were excluded. A chi-squared tests was used to compare rates of mutations between groups when appropriate.

Results/Outcomes: A total of 139 patients were identified. The median overall age was 57 years (IQR: 48-68) and 34% were female. The majority of the cohort was White (n=98, 71%), 22% were Black (n=30), and 8% were grouped as an Other race category (n=11). The most common overall mutation was TP53 (78%), followed by APC (74%), KRAS (42%), PIK3CA (17%), NRAS (6%), and BRAF (4%). Rates of KRAS mutations (50 vs. 38%), PIK2CA (20 vs. 17%), TP53 (81 vs. 75%), and BRAF (7 vs. 4%) were higher among Black patients when compared to white patients (Figure). Conversely, NRAS mutations were higher among White patients (7 vs 3%). A third of patients (n=44, 32%) were considered early onset rectal cancer patients, with a median age of 43 years (IQR: 35-47). Among this group 66% were White (n=29), 28% were Black, and 7% Other race. The rate of KRAS mutations was significantly higher in the early onset group (57 vs. 36%, p=0.019), driven by high rates among Black patients diagnosed prior to the age of 50 (75 vs 33%) (Figure). Other detailed trends of mutations by race and age at onset can be found in the Figure.

Conclusion/Discussion: In this single institutional cohort, genetic mutational differences exist between patients diagnosed early onset rectal cancer and those diagnosed after the age of 50. We found that there are differences in genetic mutation patterns by race, particularly in rates of KRAS, however these need to be confirmed in a larger patient cohort. Future multi-institutional studies should aim to focus on the prognostic significance of these mutations, impact on treatment, disease free survival, and recurrence patterns.