Correlation of K-ras codon 12 mutations in human feces and ages of patients with colorectal cancer (CRC)

Abstract

Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and constitutes a major medical and economic burden worldwide. A thorough understanding of the oncogenes or genes related to tumorigenesis is the key to developing successful therapeutic strategies. Molecular analysis of feces constitutes a potentially potent and noninvasive method for detection of CRC. Using nested reverse transcription-polymerase chain reaction (RT-PCR) and amplified restriction fragment length polymorphism analysis, sloughed cells from the entire length of the colon and rectum were analyzed for expression of activating K-ras codon 12 mutants, which are becoming attractive targets for antisense treatment. K-ras codon 12 mutant sequences were detected in feces of 5% (1/20) of healthy controls, in feces of 41% (12/29) of CRC patients, in 10% (3/29) of isolates of tissue complementary DNA (cDNA), and in 14% (4/29) of isolates of genomic DNA. Age of patient was significantly associated with K-ras codon 12 sequences in feces: Patients with wild-type K-ras codon 12 sequences were significantly younger than those with mutated forms of K-ras codon 12. Fecal ribonucleic acid (RNA) analysis was demonstrated to be a useful for diagnosis of CRC. This technique may be suitable for screening and determining the clinical significance of active mutations of the K-ras gene in feces and would possibly be useful for identifying patients that would benefit from antisense therapy.