KRAS Variant Frequency and Colorectal Cancer–Specific Survival by Race and Ethnicity

Importance: Colorectal cancer is the third most commonly diagnosed cancer and the third leading cause of cancer-associated deaths in the US. Hispanic and non-Hispanic Black patients experience higher colorectal cancer mortality rates compared with non-Hispanic White patients. More data are needed to understand the role of cancer biology in colorectal cancer survival disparities among racial and ethnic minority groups. Objective: To evaluate racial and ethnic differences in KRAS variant frequency and the association of presence of a KRAS variant with colorectal cancer-specific survival. Design, Setting, and Participants: This population-based cross-sectional study used data from the Surveillance, Epidemiology, and End Results Program and included patients diagnosed with colorectal cancer from 2010 through 2015, with follow-up through December 31, 2018. Data were analyzed between December 2023 and August 2024. Exposure: Racial and ethnic differences in KRAS variant frequency. Main Outcomes and Measures: Outcomes of interest were cumulative incidence of colorectal cancer-specific death, assessed using cumulative incidence functions, and subdistribution hazard ratio (sHR) for colorectal cancer-specific death, assessed using Fine-Gray regression models. Results: A total of 21 354 patients (mean [SD] age at diagnosis, 62.54 [13.78] years; 9653 females [45.2%]; median [IQR] follow-up, 2.67 [1.25-4.17] years) were included in the analysis, including 1680 Asian or Pacific Islander patients (7.8%), 2459 Hispanic patients (11.5%), 2761 non-Hispanic Black patients (12.9%), and 14 454 non-Hispanic White patients (67.7%). Hispanic patients and non-Hispanic Black patients had higher KRAS variant frequencies than non-Hispanic Asian or Pacific Islander patients and non-Hispanic White patients (44.2% and 48.3% vs 37.5% and 39.3%, respectively). Among patients with KRAS wild-type tumors, the unadjusted cumulative incidence of colorectal cancer-specific death was highest for Hispanic patients (59.5%; 95% CI, 55.4%-63.3%; P < .001); among patients with KRAS variant tumors, colorectal cancer-specific death was highest for non-Hispanic Black patients (67.3%; 95% CI, 63.3%-70.9%; P < .001). Among patients with KRAS wild-type tumors, Hispanic patients showed a significantly increased risk of colorectal cancer-specific death (sHR, 1.11; 95% CI, 1.01-1.22; P = .03). Among patients with KRAS variant tumors, non-Hispanic Black patients had a significantly increased risk of colorectal cancer-specific death (sHR, 1.18; 95% CI, 1.07-1.29; P < .001). Conclusions and Relevance: In this cross-sectional study of patients with colorectal cancer, Hispanic patients and non-Hispanic Black patients had higher KRAS variant prevalence than non-Hispanic White patients. Among patients with a KRAS variant, non-Hispanic Black patients had worse cause-specific survival than non-Hispanic White patients. Among patients with wild-type KRAS, Hispanic patients had worse survival compared with non-Hispanic White patients. These findings highlight the need for further research on racial and ethnic differences in KRAS-related outcomes.