Cyclooxygenase-2 (COX2) gene polymorphisms and the risk of sporadic colorectal cancer and polyps among Jordanian population.

BACKGROUND/AIMS: Cyclooxygenase-2 (COX2) is a crucial enzyme involved in the metabolism of Prostaglandins and it has been implicated in several processes. This study was done to investigate the associations of polymorphisms in COX2 gene with the risk of colorectal cancer or polyps development among Jordanian population and to correlate with other ethnicities. MATERIALS AND METHODS: One hundred and thirty five cases (135) of colorectal carcinoma were studied for COX2 -A1195G polymorphisms employing PCR-RFLP technique, in addition to 104 cases of adenomatous polyps and 115 matched controls taken from the general population. RESULTS: Sixty eight colorectal cancer patients were males and 67 of patients were females with a median age of (58.0±13.9 year). Sixty six (66) of polyp cases were males and 38 were females with a median age of (58.1±14.16). The A-1195G AA carriers were 3.1 times less likely to develop CRC (95% CI: 1.8-5.3, p<0.0001), and 1.8 times less likely to develop polyps (95% CI: 0.99-3.2, p=0.056).The A-1195G AG carriers were at higher risk to develop cancer in a dose dependent manner. The AG carriers were 2.9 time more likely to develop CRC and two times more likely to develop polyps when compared to controls. The A allele was more predominant in controls than in polyps or CRC cases. Carriers of the A allele were 1.6 times less likely to develop polyps and 2.6 times less likely to develop CRC. CONCLUSION: The presence of the COX-2 -1195AA genotype may protect against risk of developing colorectal cancer.

Allele and genotype frequencies of the polymorphic methylenetetrahydrofolate reductase and colorectal cancer among Jordanian population.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA synthesis and repair. We here aimed to investigate two common polymorphisms, C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer (CRC) cases among Jordanian. MATERIALS AND METHODS: 131 CRC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the general population, employing the PCR-RFLP technique. RESULTS: We found the frequency of the three different genotypes of MTHFR C677T among Jordanians to be CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3% among controls. Carriers of the TT genotype were less likely to have CRC (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype. Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant association between genetic polymorphism at this site and CRC. Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the TA haplotype (677T-1298A) between cases and controls. The TA haplotype was associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9, p=0.03). CONCLUSIONS: The genetic polymorphism of MTHFR at 677 and the TA haplotype may modulate the risk for CRC development among the Jordanian population. Our findings may reflect an importance of genes involved in folate metabolism in cancer risk.