vitamin-b-12 and Adenoma

Colorectal cancer and adenoma risk are inversely associated with higher total folate intake. Significant modifiers of cancer risk also include other methyl-related nutrients and alcohol. Adequate folate intake is particularly important for women at higher risk for breast cancer because of moderate alcohol consumption. The methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism is associated with a reduced risk of some forms of cancer. The protective effect of this folate-related polymorphism is dependent on adequate folate status. Cancer risk may be increased in individuals with the homozygous genotype for the MTHFR 677C-->T polymorphism who have low status of methyl-related nutrients including folate. Intake recommendations to potentially reduce cancer risk include substitution of low folate foods with folate-dense fruits and vegetables and in countries where there is no mandatory folic acid fortification, increased consumption of folic acid from available fortified foods or supplements. Adequate dietary intake of vitamin B-6 and methionine can be achieved by consumption of low fat, concentrated food sources of these nutrients. The recommended intake for vitamin B-12 for individuals >/==" BORDER="0">51 y should be provided predominately in crystalline form (e.g., fortified ready-to-eat cereal, supplements). If alcohol is consumed, consumption should be restricted to <15 g/d or <1 drink/d. The negative effects of low intakes of the methyl-related nutrients with high intakes of alcohol are additive, therefore changes in overall dietary patterns to ensure the consumption of a protective high methyl diet are recommended.

Topics: Adenoma; Alcohol Drinking; Colonic Neoplasms; Folic Acid; Humans; Methylation; Methylenetetrahydrofolate Reductase (NADPH2); Mutation, Missense; Neoplasms; Nutrition Policy; Polymorphism, Single Nucleotide; Risk Factors; Vitamin B 12

The purpose of this review is to outline the principal mechanisms involved in folate metabolism and how they may relate to the pathogenesis of colorectal cancer (CRC). In recent years, mild folate depletion (low normal level) has been associated with an increased risk of developing certain cancers, in particular colorectal neoplasia. The epidemiologic and mechanistic evidence linking folate deficiency with carcinogenesis is reviewed, with a particular emphasis on colorectal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is a critical folate metabolizing enzyme, and a functional polymorphic variant of this enzyme, the so-called thermolabile variant, caused by a C677T transition in the MTHFR gene, is common in the general population. This review critically examines the evidence that suggests that carriers of this C677T variant may be at increased risk of developing colorectal neoplasia. Although folate depletion may predispose to the initiation of the neoplastic process, folate supplementation, on the other hand, might potentiate the progression of an already established early neoplastic clone (eg, a colorectal adenoma). This could have potential public health implications, given an increasingly widespread policy of folate supplementation of food staples.

Topics: Adenoma; Animals; Colorectal Neoplasms; Dietary Supplements; DNA Methylation; DNA, Neoplasm; Folic Acid; Folic Acid Deficiency; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Oxidoreductases Acting on CH-NH Group Donors; Vitamin B 12

Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.. The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Participants were randomly assigned to receive a combination pill of folic acid (2.5mg), vitamin B(6) (50mg), and vitamin B(12) (1mg) or placebo. This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up. We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors. All statistical tests were two-sided.. The risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20). Treatment was not associated with the risk of adenoma when data were analyzed by subsite, size, stage, and the number of adenomas. There was no statistically significant effect modification by alcohol intake, history of cancer or adenoma, or baseline plasma levels or intakes of folate, vitamin B(6), or vitamin B(12).. Our results indicate no statistically significant effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on colorectal adenoma among women at high risk for cardiovascular disease.

Topics: Adenoma; Adult; Aged; Anticarcinogenic Agents; Cardiovascular Diseases; Colorectal Neoplasms; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Follow-Up Studies; Humans; Incidence; Linear Models; Male; Middle Aged; Poisson Distribution; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6

Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas.. The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association.. We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas.. Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.

Topics: Adenoma; Alcohol Drinking; Aspirin; Chemoprevention; Colorectal Neoplasms; Double-Blind Method; Female; Folic Acid; Genotype; Humans; Incidence; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Neoplasm Recurrence, Local; Poisson Distribution; Polymorphism, Genetic; Riboflavin; Risk; Surveys and Questionnaires; Vitamin B 12; Vitamin B 6

The role of folate one-carbon metabolism in colorectal cancer development is controversial, with nutritional intervention studies producing conflicting results. It has been reported that Apc

Topics: Adenoma; Animals; Choline; Diet; Folic Acid; Intestinal Neoplasms; Methionine; Mice; Mice, Inbred C57BL; Mice, Transgenic; Random Allocation; Vitamin B 12

Radioiodine administered for the treatment of hyperthyroidism and thyroid cancer can be taken up by many non-thyroid tissues which express sodium iodide symporter. Though gastric mucosa takes up radioiodine, its impact on parietal cell has not been evaluated. The aim of the present study was to compare vitamin B12 and homocysteine concentrations in patients with thyroid disorders treated by radioiodine ablation with those in control population without radioiodine exposure.. Patients with Graves' disease, toxic multinodular goiter (TMNG), toxic adenoma (TA) or differentiated thyroid cancer (DTC) who had received 131I were included as "patients". Healthy persons and patients having Graves' disease but without exposure to radioiodine were recruited as "controls". A total of 35 patients and 35 controls were included. Patients were divided into Graves' disease and non-Graves' disease (TMNG, TA, DTC) groups. Graves' disease patients were compared with Graves' disease controls while non-Graves' disease patients were compared with healthy controls.. In the Graves' disease group, median vitamin B12 concentration was 240 pg/ml (IQR: 148 - 371) in patients (n=23) and 195 pg/ml (IQR: 140 - 291 pg/ml) (p=0.13, ns) in controls (n=24). In the non-Graves' disease group, median serum vitamin B12 concentration was 147 pg/ml (IQR: 124 - 325pg/ml) in patients (n=12) and 190 pg/ml (IQR: 157 - 373 pg/ml) (p=0.34, ns) in healthy controls (n=11). Homocysteine concentrations were also similar in compared groups of patients and controls.. Radioiodine ablation does not cause vitamin B12 deficiency. However, a prospective study with a larger number of patients is required to confirm this finding.

Topics: Adenoma; Adult; Aged; Carcinoma, Papillary, Follicular; Case-Control Studies; Cross-Sectional Studies; Female; Goiter, Nodular; Graves Disease; Homocysteine; Humans; Iodine Radioisotopes; Male; Middle Aged; Thyroid Neoplasms; Vitamin B 12

Topics: Adenoma; Anticarcinogenic Agents; Cardiovascular Diseases; Colorectal Neoplasms; Female; Folic Acid; Humans; Male; Vitamin B 12; Vitamin B 6

There are no data regarding basal folate levels in patients without colorectal adenoma. This study aimed to determine the minimum serum folate concentration that associates with reduced risk of colorectal adenoma.. 1510 consecutive patients underwent total colonoscopy for suspected colorectal lesions after barium enema examination. Prior to colonoscopy, history of alcohol consumption was noted and blood serum analyzed for folate and vitamin B12 levels. Polypoid lesions were evaluated histologically. We excluded patients with anemia, history of colonoscopy, overconsumption of alcohol, or malignancies. In all, 458/1510 patients (male/female; 258/200, 40-75 years) were determined eligible. Variables were compared between patients with adenoma and those without adenoma.. Serum folate concentration was the variable with the most significant statistical variation between males with adenoma (8.0 ng/ml) and males without adenoma (9.2) (p = 0.001). Serum folate concentrations in females with adenoma did not differ significantly from those in females without adenoma (10.7 versus 10.9). When subjects were stratified into groups according to serum folate, we found no significant difference in the prevalence of adenoma in patients with folate levels greater than 8.0 ng/ml.. Patients with serum folate concentrations above 8.0 ng/ml had the lowest risk of developing colorectal adenoma.

Topics: Adenoma; Adult; Aged; Colorectal Neoplasms; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Hospitals, Teaching; Humans; Japan; Male; Mass Screening; Middle Aged; Prevalence; Prospective Studies; Risk; Sex Factors; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B(6) may lower risk of colorectal cancer by preventing aberrations in one-carbon metabolism or by anti-inflammatory effects. We prospectively evaluated the association between plasma levels of pyridoxal 5'-phosphate (PLP; the active form of vitamin B(6)) and risk of colorectal cancer in a nested case-control study within the Physicians' Health Study. Among 14,916 men who provided blood specimens in 1982 to 1984, we identified 197 incident colorectal cancer cases through 2000 and individually matched them to 371 controls by age and smoking status. Plasma PLP levels were positively correlated with cold cereal intake and plasma levels of folate and vitamin B(12) (age- and smoking-adjusted partial correction r = 0.28-0.48) and slightly inversely correlated with body mass index (r = -0.11) and plasma levels of homocysteine, C-reactive protein, tumor necrosis factor-alpha receptor 2, and interleukin-6 (r = -0.23 to -0.14). With control for these factors and known risk factors for colorectal cancer, plasma PLP levels were significantly inversely associated with risk of colorectal cancer; compared with men in the lowest quartile, those with PLP in quartiles 2 to 4 had relative risks (95% confidence interval) of 0.92 (0.55-1.56), 0.42 (0.23-0.75), and 0.49 (0.26-0.92; P(trend) = 0.01), respectively. In conclusion, vitamin B(6) may protect against colorectal cancer independent of other one-carbon metabolites and inflammatory biomarkers.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Case-Control Studies; Colorectal Neoplasms; Folic Acid; Humans; Incidence; Interleukin-6; Male; Middle Aged; Physicians; Prospective Studies; Pyridoxal Phosphate; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 6

Thymidylate synthase and serine hydroxymethyltransferase are involved in folate metabolism. In a case-control study, including 768 cases and 709 controls, we investigated the associations between colorectal adenomas and TS tandem repeat and SHMT1 C1420T polymorphisms, and the interplay with B-vitamins. The polymorphisms were not associated with adenomas, but there was a borderline significant interaction between TS genotype and vitamin B6: the association between vitamin B6 and adenomas seemed positive in TS 3R/3R individuals, but inverse in TS 2R/2R individuals. This study does not provide evidence for a role of SHMT1 genotype in adenoma occurrence. Future research has to indicate whether the TS-B6 interplay is a real effect or a chance finding.

Topics: Adenoma; Aged; Case-Control Studies; Colorectal Neoplasms; Diet; Folic Acid; Glycine Hydroxymethyltransferase; Humans; Middle Aged; Netherlands; Polymorphism, Genetic; Riboflavin; Risk Factors; Thymidylate Synthase; Vitamin B 12; Vitamin B 6; Vitamin B Complex

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.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Black or African American; Case-Control Studies; Colonic Polyps; Colorectal Neoplasms; DNA Methylation; Female; Folic Acid; Genes, APC; Homocysteine; Humans; Male; Middle Aged; Promoter Regions, Genetic; Smoking; Tetrahydrofolates; Vitamin B 12; Vitamins

Dietary folate and alcohol consumption as well as polymorphic variants in one-carbon metabolism genes may modulate risk of colorectal adenoma through aberrant DNA methylation and altered nucleotide synthesis and repair. We assessed the association of 24 non-synonymous single nucleotide polymorphisms (nsSNPs) in 13 genes in the one-carbon metabolism pathway and risk of colorectal adenoma in 556 incident cases and 557 controls nested in the Nurses' Health Study. Most of the SNPs were not associated with risk of colorectal adenoma. We did, however, observe a modest increased risk among carriers of the transcobalamin (TCN) II 259 Pro/Arg + Arg/Arg variant (odds ratio 1.48, 95% confidence interval 1.09-2.02) for colorectal adenoma. The TCN II Pro259Arg polymorphism may affect TCN binding and transport of vitamin B(12) and thus warrants further investigation of its biological function. In addition, the methionine synthase reductase (MTRR) Arg415Cys and MTRR Ser284Thr variant carriers, also in the vitamin B(12) pathway, have suggestive associations with advanced colorectal adenoma (defined as being larger than 1 cm, villous, tubular-villous or carcinoma in situ histology). We observed significant evidence for departure from multiplicative interaction for the betaine-homocysteine methyltransferase (BHMT) Arg239Gln with dietary methyl status (based on intake of dietary folate, methionine and alcohol intake) in relation to colorectal adenoma; no such interaction was observed for the other 23 SNPs. Further investigation is required to validate the association of the polymorphisms in the one-carbon metabolic genes and risk of colorectal adenoma.

Topics: Adenoma; Adult; Alcohol Drinking; Betaine-Homocysteine S-Methyltransferase; Case-Control Studies; Colorectal Neoplasms; Diet; Female; Ferredoxin-NADP Reductase; Folic Acid; Genetics, Population; Humans; Methionine; Middle Aged; One-Carbon Group Transferases; Polymorphism, Single Nucleotide; Prospective Studies; Risk; Transcobalamins; Vitamin B 12

Greater promoter methylation in some tumor-suppressor genes underlies most sporadic colorectal cancers and increases with age in the colon.. We tested the hypothesis that biomarkers of folate and vitamin B-12 status are associated with estrogen receptor alpha (ERalpha) and mutL homolog 1 (MLH1) promoter methylation in subjects with and without neoplasia.. Biopsies of normal-appearing colorectal mucosa from 156 subjects with and without colorectal neoplasia (disease free, n = 76; cancer, n = 28; adenoma, n = 35; hyperplastic polyps, n = 17) were obtained at colonoscopy and used to evaluate methylation in 7 CpG sites in the ERalpha promoter and 13 CpG sites in the MLH1 promoter. Blood samples were obtained for the measurement of serum and red cell folate, serum vitamin B-12, and plasma homocysteine concentrations. Methylation indexes were generated to reflect an average methylation value across all CpG dinucleotides in both ERalpha and MLH1.. The methylation indexes for ERalpha and MLH1 generally were significantly (P < 0.05) higher in subjects with neoplasia than in disease-free subjects. The ERalpha methylation index correlated negatively with serum vitamin B-12 (r = -0.239, P = 0.003) and positively with plasma homocysteine (r = 0.188, P = 0.021). Disease status (P < 0.005), age (P < 0.001), and serum vitamin B-12 concentrations (P = 0.006) were independent determinants of ERalpha promoter methylation. Serum and red cell folate concentrations had no influence on ERalpha promoter methylation.. Serum vitamin B-12 but not folate status may be associated with ERalpha promoter methylation in normal-appearing colorectal mucosa.

Topics: Adaptor Proteins, Signal Transducing; Adenoma; Aged; Base Sequence; Biomarkers; Case-Control Studies; Colon; Colonic Polyps; Colorectal Neoplasms; DNA Methylation; Erythrocytes; Estrogen Receptor alpha; Female; Folic Acid; Homocysteine; Humans; Intestinal Mucosa; Male; Middle Aged; MutL Protein Homolog 1; Nuclear Proteins; Nutritional Status; Vitamin B 12

Decreased dietary intakes of calcium, vitamin D and folic acid have been suggested as risk factors for human colon cancer. We previously fed a Western-style diet (WD) containing reduced calcium, vitamin D and increased fat content to normal C57/Bl6 mice: hyperproliferation, hyperplasia and whole crypt dysplasias developed in the colon following WD administration. Utilizing the same diet, we now also decreased the levels of several nutrients that are required for biochemical reactions involving methyl group inadequacy, i.e. folic acid, methionine, choline and vitamin B(12). Dietary levels of these nutrients were reduced to nutrient-density levels approximating those consumed by large segments of human Western populations. This further modification of the WD resulted in adenoma and carcinoma development in normal mouse colon (P < 0.04 compared with AIN-76A diet). The results indicate, for the first time, that a semi-purified rodent diet designed to mimic the human Western diet can induce colonic tumors in normal mice without carcinogen exposure.

Topics: Adenoma; Animals; Body Weight; Bromodeoxyuridine; Cell Division; Choline; Colonic Neoplasms; Diet; Dietary Fats; Epithelium; Female; Folic Acid; Immunoenzyme Techniques; Intestine, Large; Liver; Male; Methionine; Methylation; Mice; Mice, Inbred C57BL; Vitamin B 12

Topics: Adenoma; Adolescent; Aged; Anemia, Pernicious; Antibodies, Anti-Idiotypic; Antibody Formation; Autoantibodies; Autoimmune Diseases; Blood Protein Electrophoresis; Coombs Test; Diabetes Complications; Erythrocytes; Female; Humans; Male; Middle Aged; Pancreatitis; Rheumatic Heart Disease; Syphilis; Thymoma; Thyroid Diseases; Thyroid Neoplasms; Tuberculosis; Vitamin B 12

Topics: Adenoma; Cobalt Isotopes; Corrinoids; Geriatrics; Humans; Methionine; Pancreas; Parathyroid Glands; Parathyroid Neoplasms; Photography; Radioisotopes; Radionuclide Imaging; Selenium; Vitamin B 12