title: Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes.
abstract: Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.
authors.affiliation: King Faisal Specialist Hospital Research Centre, Oncology, Jeddah, Saudi Arabia jmzekri@hotmail.com.|College of Medicine, Al-Faisal University, Saudi Arabia jmzekri@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Zekri
authors.affiliation: National Guard Hospital, Oncology, Jeddah, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Al-Shehri
authors.affiliation: King Fahad Hospital, Oncology, Madinah, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Mahrous
authors.affiliation: National Guard Hospital, Oncology, Jeddah, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Al-Rehaily
authors.affiliation: King Abdullah Medical City and Oncology Center, Oncology, Jeddah, Saudi Arabia.
authors.forename: T
authors.initials: T
authors.lastname: Darwish
authors.affiliation: King Faisal Specialist Hospital Research Centre, Oncology, Jeddah, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Bassi
authors.affiliation: King Abdullah Medical City, Oncology, Mekkah, Saudi Arabia.
authors.forename: H
authors.initials: H
authors.lastname: El Taani
authors.affiliation: King Abdullah Medical City, Oncology, Mekkah, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Al Zahrani
authors.affiliation: King Abdullah Medical City, Oncology, Mekkah, Saudi Arabia.|Oncology Centre, Mansoura University, Mansoura, Egypt.
authors.forename: S
authors.initials: S
authors.lastname: Elsamany
authors.affiliation: King Faisal Specialist Hospital Research Centre, Oncology, Jeddah, Saudi Arabia.|Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: J
authors.initials: J
authors.lastname: Al-Maghrabi
authors.affiliation: King Faisal Specialist Hospital Research Centre, Oncology, Jeddah, Saudi Arabia.
authors.forename: B B
authors.initials: BB
authors.lastname: Sadiq
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018912:Arabs / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D012529:Saudi Arabia; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)