Dietary
folate status appears to influence risk for
colorectal cancer possibly by alterations in DNA methylation and
nucleotide precursor pools. Polymorphisms (677C-->T and 1298A-->C) in
methylenetetrahydrofolate reductase (MTHFR), a key
enzyme in
folate metabolism, determines
enzyme activity. The frequency of polymorphisms in the gene varies extensively in different populations. We sought to determine the association between
folate status,
folate metabolism, DNA methylation, tobacco, alcohol consumption, and the risk of colorectal
adenomas in African Americans. Among 58 patients who underwent a clinically indicated colonoscopy, 23 patients with histology confirmed colorectal
polyps and 35 patients without were recruited for a case-control study. Blood samples were collected from fasting patients for determination of serum and red blood cell (RBC)
folate,
homocysteine,
vitamin B(12), and methylation status. Polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) technique was performed to identify the MTHFR 677 C-->T polymorphism and specific PCR was used to analyze
adenomatous polyposis coli (APC) gene-promoter sequence methylation. Among 23 cases, 49
polyps (adenomatous, n = 41 and hyperplastic, n= 8) were identified. Twenty-eight (57%) of the
polyps were on the left side and 21 (42%) were on the right side of the colon. There was no association between the presence of colon
polyps and levels of
folate (serum, RBC),
vitamin B(12), or
homocysteine. Forty-eight individuals (84%) were homozygous for 677 CC. Of these individuals, 18 (37.5%) had >/=1 colorectal
polyps, whereas 30 (62.5%) had no
polyps. Nine individuals were heterozygous for 677 CT, and 4 (44%) of these individuals had colon
polyps. Eighty-eight percent of the APC gene-promoter sequences tested using peripheral blood
DNA from patients were unmethylated. Among the individuals who showed APC methylation, 66% had
polyps; 33% were
polyp free using their blood
DNA. There was highly significant association between smoking and alcohol consumption with the presence of a colon
polyp (P= .0006 and P= .05, respectively). In conclusion, the lack of the 677 TT may be a significant risk factor for
colon neoplasm in the African-American population. Smoking and alcohol consumption were found to be risk factors for colon
polyps. APC gene-promoter sequence methylation found in peripheral blood may be an
indicator of risk for
polyp formation and an important screening tool.