BACKGROUNDThe few studies of the molecular biology of colorectal cancer (CRC) in Middle Eastern populations have included only small samples of patients.OBJECTIVEEvaluate the frequency and prognostic effect of RAS, BRAF, PIK3CA, PTEN, and EGFR somatic mutations as well as mismatch repair (MMR) deficiency in Lebanese Middle Eastern patients.DESIGNRetrospective single-center descriptive study.SETTINGLebanese Middle Eastern patients in a tertiary medical center.METHODSWe included all patients diagnosed with CRC between January 2010 and December 2015, in whom RAS mutational status and the expression of MLH1 and MSH2 proteins were available.MAIN OUTCOME MEASURESGenetic mutations detected by direct sequencing while MMR protein expression was evaluated by immunohistochemistry.SAMPLE SIZE645 patients.RESULTSRAS, BRAF, EGFR, PI3KCA, and PTEN mutation rates were 38.5%,12.9%, 0%, 11.1% and 0% respectively. The MMR deficiency rate was 20.6%. No factor was associated with RAS mutation whereas MMR-deficient tumors were less likely to be metastatic at diagnosis. Among patients with wild-type RAS females fared better than males (median overall survival [OS]=1734 vs 1079 days respectively, P=.015) even after adjustment for confounding factors by Cox regression analysis. This finding was not reproduced in the RAS-mutated group. The median OS of patients with MMR-deficient tumors was not reached, while the median OS was 2475 days in patients who had maintained expression of both MLH1 and MSH2.CONCLUSIONThe RAS mutation rate was similar to Western and East Asian countries, but not for the BRAF mutation and MMR deficiency. We also found a prognostic effect for sex in the RAS wild-type group, a finding worthy of further exploration.LIMITATIONSRetrospective, single center and small sample size. Expression of MSH6 and PMS2 not analyzed.