Assessment of Molecular-Genetic Alterations and Racial/Ethnic Disparities in Outcomes in Patients With Colon Cancer
Wendy Lee*1, Brian Mailey1, Avo Artinyan2, Xiaoming Shen1, Jianming Lu1, Marjun Philip N. Duldulao1, Julio Garcia-Aguilar1, Joseph Kim1
1City of Hope National Medical Center, Duarte, CA; 2Michael E. Debakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX
Background: We previously observed racial/ethnic disparities in survival for patients with GI cancers in Los Angeles County (LAC). However, we could not account for these disparities by standard clinicopathologic factors or socioeconomic status (SES) and access to care. Our objective was to examine potential racial/ethnic disparities in tumor biology in colon cancer patients to determine if molecular-genetic differences are associated with patient outcomes.Methods: From the LAC Cancer Surveillance Program (CSP), we identified colon cancer patients from 1988 to 2006. We grouped patients by race/ethnicity and compared clinicopathologic factors; and constructed Kaplan-Meier survival curves. We then obtained archived colon cancer specimens (n=76) from surgical patients at our institution. DNA was extracted and evaluated for BRAF, KRAS, and TP53 mutations and for microsatellite instability (MSI).Results: CSP patients included whites (n=20,809), blacks (n=5,025), Hispanics (n=5,455), and Asians (n=3,813). By Kaplan-Meier method, Asians had the longest survival (Table 1; log-rank P<0.001). Multivariate Cox regression analysis showed that race/ethnicity independently predicted survival even when controlling for disease extent, treatment, and SES. Analysis of colon cancer tissues from white, black, Hispanic, and Asian patients (n=19 for each group) showed highest frequency of BRAFV600E mutation in white and Hispanic tissues. KRAS codon 12 mutation was most frequent in Asian tissues. In addition, we observed that MSI was lowest in tissues from Asians. Conclusions: We identified racial/ethnic disparities in survival for colon cancer patients, which parallel best the detection of MSI in the corresponding racial/ethnic group. This suggests that disparities in survival could be secondary to differences in tumor biology between major racial/ethnic groups. We are coordinating a multicenter study in LAC to further investigate the potential effect of these genetic alterations on clinical outcomes.
Table 1. Survival data and molecular analysis for colon cancer patients
| CSP data | Frequency of genetic alterations | |||
| Race/ethnicity | Median survival (months) | BRAFV600E mutation | KRAS codon 12 mutation | MSI |
| White | 71 | 21% | 26% | 11% |
| Black | 52 | 5% | 21% | 26% |
| Hispanic | 81 | 16% | 32% | 7% |
| Asian | 107 | 0% | 53% | 0% |
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