Risk factors for K-RAS proto-oncogene mutation in colorectal cancer

ABSTRACT

K-rats is an important onco-gene on chromosome 12 and encodes p21 Ras-protein, which is a growth promoting protein. Specific point mutations in codons 12 and 13 are prevalent in colorectal cancer [CRC] patients. Recognition of K-ras mutations may be helpful in screening and early diagnosis of CRC. This study aimed at investigating the association between potential variables known or suspected to be related to risk of CRC and occurrence of K-ras mutations, explaining how such variables play a role in CRC tumorigenesis. Eighty CRC patients were examined for RBC folic acid by enzyme chemi-luminescence and K-ras proto-oncogene genotyping for codon 12 mutations by enriched PCR-RELP technique. RBC folic acid level was significantly deficient in CRC patients with K-ras mutation [23 patients, mean RBC folate= 100.96+51.3 ng/ml] than those without the mutation [57 patients, mean RBC folate = 216.6+116.4 ng/ml][P<0.01], suggesting that decreased folic acid may be a risk factor for K-ras mutation development. Gender also was found to be another predicting risk factor, in spite of being masked by the accentuated folic acid deficiency in females. Folic acid supplementation should be mandatory, and those at high-risk of CRC should be screened for the risk of K-ras mutation using the prediction equation method depending on sex and RBC folate followed by close monitoring for those a high risk for the mutation