Racial disparity in KRAS mutation frequency and outcomes in colorectal cancer (CRC): A U.S. population based study.

Abstract

18 Background: Racial disparity in CRC survival outcome is well documented. Although the reasons for disparity are unclear, a combination of differences in access to care, quality of care, differential treatment response, and underlying cancer biology are implicated. Further, recent studies have observed differences in KRAS mutation frequency between race/ethnic groups. KRAS mutation in metastatic CRC portends a worse response to EGFR-directed therapy, and predicts a poorer prognosis. In this study, we examined whether racial/ethnic differences in KRAS mutation frequency might impact CRC outcomes on a population-based level. Methods: We examined data from 202,237 CRC patients in the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The differences in tumor mutation status by stage and race/ethnicity were examined by χ2 testing. Cause-specific survival (CSS) and overall survival by mutation status were plotted by Kaplan-Meir curves. A multivariable Cox-proportional hazards model was used to construct hazard ratios and 95% confidence intervals (CI) using patient demographics, tumor characteristics, and KRAS mutation status. Results: Overall, about 9% of patients (n = 18,248) in the SEER registry had KRAS status available. In this cohort, tumors from Non-Hispanic Black (NHB) (48%) or Hispanic patients (44%) carried a greater KRAS mutation (mKRAS) rate when compared against Non-Hispanic White (NHW) (39%) or Asian or Pacific Islander (API) patients (37%) (p < 0.01). The assessment of the impact of mKRAS within each race/ethnic group, comparing patients with mKRAS versus wild-type KRAS (wKRAS) on CSS risk show a 7% risk increase for NHW, (HR = 1.07; 95%CI:1.02-1.12), a 15% risk increase for NHB, (HR = 1.15; 95%CI:1.04-1.26) and no significant increase among API, (HR = 1.02; 95%CI:0.92-1.4). Among patients with wKRAS, with NHW for reference, the risk of CSS is 11% higher among NHB (HR = 1.11; 95%CI:1.00-1.23), 14% higher for Hispanic, (HR = 1.14; 95%CI:1.02-1.26) and no significant difference observed among API, (HR = 1.03; 95%CI:0.91-1.16). Evaluation of the interaction between race/ethnicity and KRAS status on the CSS risk shows an increase of: 11% for mKRAS NHW, (HR = 1.11; 95%CI:1.00-1.23), 13% risk for NHB (HR = 1.13; 95%CI:1.01-1.25), 11% for Hispanic wKRAS, (HR = 1.11; 95%CI:1.04-1.18), 31% for Hispanic mKRAS (HR = 1.31; 95%CI:1.18-1.145), 16% for wKRAS API (HR = 1.16; 95%CI:1.03-1.29). In contrast, no significant difference in risk is seen for NHB nor API patients, HR = 1.02 (95%CI:0.90-1.14) and 1.04 (95%CI:0.91-1.20) respectively. Conclusions: mKRAS, compared to wKRAS, connotes worse CSS among NHW and NHB patients. Among wKRAS, NHB and Hispanic patients still experience higher mortality risk. This data suggests the negative prognosis heretofore associated with mKRAS may be linked to race/ethnicity and worthy of further study.