Affiliations: [a] Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA | [b] Georgia Regents University Cancer Center, Section of Hematology/Oncology, Department of Medicine, Medical College of Georgia, Augusta, GA, USA
Correspondence:
[*]
Corresponding author: Temitope O. Keku, University of North Carolina, 103 Mason Farm Road, 7340 Medical Biomolecular Research Building, CB # 7032, Chapel Hill, NC 27599-7032, USA. Tel.: +1 919 966 5828; Fax: +1 919 843 6899; E-mail: [email protected].
Abstract: Background and Objective:African Americans have worse outcomes in colorectal cancer (CRC) than Caucasians. We sought to determine if KRAS, BRAF and PIK3CA mutations might contribute to the racial differences in CRC outcome. Methods:DNA was extracted from tissue microarrays made from CRC samples from 67 African Americans and 237 Caucasians. Mutations in KRAS, BRAF, and PIK3CA were evaluated by PCR sequencing. We also examined microsatellite instability (MSI) status. Associations of mutation status with tumor stage and grade were examined using a logistic regression model. Cox proportional hazards models were used to estimate the all-cause mortality associated with mutational status, race and other clinicopathologic features. Results:KRAS mutations were more common in African Americans than among Caucasians (37% vs 21%, p=0.01) and were associated with advanced stage (unadjusted odds ratio (OR)=3.31, 95% confidence interval (CI) 1.03–10.61) and grade (unadjusted OR=5.60, 95% CI 1.01–31.95) among African Americans. Presence of BRAF mutations was also positively associated with advanced tumor stage (adjusted OR=3.99, 95%CI 1.43–11.12) and grade (adjusted OR=3.93, 95%CI 1.05–14.69). PIK3CA mutations showed a trend toward an association with an increased risk of death compared to absence of those mutations (adjusted for age, sex and CRC site HR=1.89, 95% CI 0.98–3.65). Among African Americans, the association was more evident (adjusted for age, sex and CRC site HR=3.92, 95% CI 1.03–14.93) and remained significant after adjustment for MSI-H status and combined education-income level, with HR of 12.22 (95%CI 1.32–121.38). Conclusions:Our results suggest that African Americans may have different frequencies of somatic genetic alterations that may partially explain the worse prognosis among African Americans with CRC compared to whites.
