Clinico-pathological study of K-ras mutations in colorectal tumors in Saudi Arabia

Aims and background. K-ras gene mutations contribute to the pathogenesis of colorectal cancer. We characterized K-ras mutations in colorectal tumors in patients in the,Kingdom of Saudi Arabia, in terms of geographic area, age, gender, histology, stage, and anatomical localization. Methods. Medical records and paraffin-embedded tumor samples from 150 consecutive patients with histologically proven colorectal adenocarcinoma referred to two centers in Saudi Arabia were analyzed using an LCD-array kit. Results. K-ras mutations occurred in 56% of the patients; 48.7% of the mutations were in codon 12, most commonly p.G12V and p.G12D (each 35.6% of codon 12 mutations). Codon 13 mutations occurred in 7.3% of tumors: of these, most were p.G13D (90.9%) with the remainder p.G13R (9.1%). Codon 12 mutations overall were associated significantly with stage IVb tumors (P = 0.022) and rectal tumors (P = 0.028), with a trend of an association with a sigmoid location (P = 0.054). The p.G12V mutation was significantly associated with sigmoid tumors (P = 0.021) and negatively associated with left-sided tumors (P = 0.011), with a trend of an association with age >= 70 years (P = 0.062) and rectal tumors (P = 0.063). Other clinicopathological features were not significantly associated with K-ras mutations. Conclusions. K-ras mutations are common among the Saudi colorectal cancer population, especially pG12V and pG12D in codon 12, and are more frequent in sigmoid and rectal adenocarcinomas and stage IVB tumors.