Association of folate intake, dietary habits, smoking and COX-2 promotor −765G > C polymorphism with K-ras mutation in patients with colorectal cancer

BackgroundUnderstanding the role of environmental and molecular influences on the nature and rate of K-ras mutations in colorectal neoplasms is crucial. COX-2 polymorphisms −765G > C may play a role in carcinogenic processes in combination with specific life-style conditions or dependent on the racial composition of a particular population.If mutational events play an important role in colorectal carcinogenesis sequence, one can hypothesize that modification of these events by life-style or other factors would be a useful prevention strategy.Aim of workTo explore the association between K-ras mutation and potential variables known or suspected to be related to the risk of colorectal cancer (CRC) as well as determining the possible modulating effect of the COX-2 polymorphism, −765G > C.Subjects and methodsThe study was conducted on 80 patients with colorectal cancer from Tropical Medicine and Gastrointestinal Tract endoscopy Departments and those attending clinic of the National Cancer Institute, Cairo University during the period extending from April 2009 to March 2010.Full history taking with emphasis on the risk factors of interest, namely age, sex, family history, smoking and dietary history. Serum CEA and CA19-9, RBCs folic acid and occult blood in stool were done to all samples. K-ras protooncogene mutation at codon 12 (exon 1) and cyclooxygenase 2 (COX-2) −765G > C polymorphism were determined by PCR-RFLP.ResultsThe K-ras mutation was positive in 23 (28.7%) patients. COX-2 polymorphism revealed GG in 62.5%, GC in 26.2 % and CC genotype was found in 11.3 % of cases.The mean red blood cell folic acid level was lower in the K-ras positive group (100.96 ± 51.3 ng/ml) than the negative group (216.6 ± 166.4 ng/ml), (P < 0.01). Higher folate levels were found in males than females (median = 173 ng/ml and 85 ng/ml; respectively, P = 0.002) with adjusted odds ratio (OR) of 0.984.Only, the RBCs folate (P = 0.0018) followed by gender (P = 0.036) contributed significantly in the discrimination between patients prone to develop K-ras mutation and those who are not.ConclusionRBC folic acid was significantly deficient in CRC (colorectal cancer) patients with K-ras mutations in comparison with CRC patients free of the mutations, suggesting that folic acid may be a risk factor for K-ras mutation development.