467 PI3K Mutation in African Americans May Predict Worse Outcomes in Colorectal Cancer

Purpose: African Americans have worse outcomes in colorectal cancer (CRC) than Caucasians.Mutations in Kras, Braf and PI3K have been identified in CRC that could impact prognosis, survival or response to treatment.There is a paucity of studies looking at whether genetic alterations contribute to worse prognosis in African Americans.We sought to determine if mutations in Kras, Braf and PI3K can explain the racial differences in CRC outcome.Methods: We obtained tissue samples from 237 Caucasians and 67 African Americans from a population based study of Cancer Care Outcomes Research and Surveillance Consortium (CanCORS).CanCORS include patients who were newly diagnosed with CRC.We extracted DNA from tissue microarrays and performed polymerase chain reactions using primers for Kras codons 12 and 13, Braf exon 11, and PI3K exons 9 and 20.Somatic mutations in these genes were identified by sequencing.Mutational status, race and other clinicopathologic features were analyzed for overall survival using Cox proportional hazards model.A proportional odds model was used to examine the association between stage and grade of CRC and mutation status.Results: Frequencies of Kras mutations were higher for African Americans than Caucasians (37% vs 21%, p=0.01).We found that African Americans had significantly increased odds ratios for worse stage (OR=3.3,95%CI 1.0-11.0)and grade (OR=5.6,95%CI 1.0-31.0) of CRC if Kras mutations were present as compared to those without Kras mutations.African Americans with a PI3K mutation had higher hazard ratios for mortality than African Americans without a PI3K mutation in both univariate (HR=3.9,95%CI 1.0-14.9)and multivariate (HR=11.0,95%CI 1.4-84.8)models.Further, African Americans with PI3K mutation showed a trend toward worse overall survival when compared to Caucasians with or without PI3K mutation or African Americans without PI3K mutations (p=0.09).When adjusted for smoking, patients with Braf mutations had elevated odds of having worse stage (OR=2.7,95%CI 1.1-6.6)or grade (OR=5.2,95%CI 1.8-15.0) of CRC than those without mutations.Conclusions: We found that African Americans with PI3K mutations had worse overall survival and increased hazard ratios than those without PI3K mutations.These genetic alterations may contribute to the aggressive phenotype and may partially explain the worse prognosis observed in CRC in African Americans.