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

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.

To evaluate racial and ethnic differences in KRAS variant frequency and the association of presence of a KRAS variant with colorectal cancer-specific survival.

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.

Racial and ethnic differences in KRAS variant frequency.

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.

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).

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.