KRAS AND BRAF mutation rates and survival outcomes in colorectal cancer in an ethnically-diverse cohort

Abstract

Background: KRAS-mutant colorectal carcinoma (CRC) is resistant to anti-EGFR antibodies. Several studies compare the KRAS mutation rates between Caucasians and African Americans, but few studies have compared other ethnicities. Aims: To compare the KRAS and BRAF mutation rates, as well as overall survival rates, in CRC between ethnic groups. Additionally, we report on correlations between clinicopathological variables relevant to CRC. Methods: Clinicopathological data from 284 ethnically-diverse patients with CRC were retrospectively analysed at Liverpool Hospital (2014–2016). KRAS and BRAF mutations were detected using real-time PCR kits (from Qiagen). Ethnicity was determined using both country-of-birth and surname. Survival outcomes were available for 191 patients. Overall survival was defined as date-of-diagnosis to death from any cause. Patients still alive were censored at 50-months post-diagnosis. Results and conclusions: KRAS mutation frequency differed significantly between Caucasians and Asians (36.1% vs 56.4%, p=0.018), and Asians and South-Americans (56.4% vs 16.7%, p=0.016), but not between other groups (Middle-Easterners 45.7%). BRAF-V600E mutation frequency differed significantly between Caucasians and Middle-Easterners (16% vs 0%, p=0.029), but not between other groups (Asian 8.6%, South-American 16.7%). The 50-month survival rate did not differ between ethnicities (Caucasians 44%, Middle-Easterners 52%, Asians 58%, South-Americans 50%). Of patients who died, the median survival time was 28 months. Overall survival did not significantly differ between patients with wild-type and mutant KRAS. Tumours with BRAF-V600E mutations were more likely to display microsatellite instability (MSI) than tumours with wild-type BRAF (45.5% vs 8.3%, p<0.001). Tumours displaying MSI occurred more frequently in the right colon (p=0.007). KRAS mutations were more frequent in circumferential tumours (p=0.04), and tumours without vascular invasion (p=0.004).