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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Folate deficiency has been associated with dysplasia in human cancer models. Patients with ulcerative colitis commonly have decreased folate levels, which are partially due to sulfasalazine, a competitive inhibitor of folate absorption. To study the effect of folate supplementation on the risk of dysplasia or cancer (neoplasia) in ulcerative colitis, records from 99 patients with pancolitis for greater than 7 yr and enrolled in a surveillance program were reviewed. Thirty-five patients with neoplasia were compared with 64 patients in whom dysplasia was never found to determine the effect of folate supplementation on the rate of development of neoplasia using case-control methodology. At the time of the index colonoscopy, patients with neoplasia were older (43 +/- 11 vs. 39 +/- 12 yr) and had disease of longer duration (20 +/- 8 vs. 15 +/- 7 yr, p less than 0.05). Folate supplementation was associated with a 62% lower incidence of neoplasia compared with individuals not receiving supplementation (odds ratio, 0.38; 95% confidence interval, 0.12-1.20). There was no appreciable change in this effect when models were fit to adjust for sulfasalazine dose, duration of disease, age at symptom onset, prednisone dose, sulfa allergy, sex, race, or family history of colon cancer. The statistical power of the association between folate supplementation and neoplasia was 72%. Correction of risk factors before the development of neoplasia may prevent this serious complication. Pending a larger case-control study, folate supplementation during sulfasalazine administration is recommended to possibly prevent the complication of dysplasia or cancer in ulcerative colitis.
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PMID:Effect of folate supplementation on the incidence of dysplasia and cancer in chronic ulcerative colitis. A case-control study. 229 14

Folate derivatives are important in experimental colorectal carcinogenesis; low folate intake, particularly with substantial alcohol intake, is associated with increased risk. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate, required for purine and thymidine syntheses, to 5-methyltetrahydrofolate, the primary circulatory form of folate necessary for methionine synthesis. A common mutation (677C-->T) in MTHFR reduces enzyme activity, leading to lower levels of 5-methyltetrahydrofolate. To evaluate the role of folate metabolism in human carcinogenesis, we examined the associations of MTHFR mutation, plasma folate levels, and their interaction with risk of colon cancer. We also examined the interaction between genotype and alcohol intake. We used a nested case-control design within the Physicians' Health Study. Participants were ages 40-84 at baseline when alcohol intake was ascertained and blood samples were drawn. During 12 years of follow-up, we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status. We genotyped for the MTHFR polymorphism and measured plasma folate levels. Men with the homozygous mutation (15% in controls) had half the risk of colorectal cancer [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.87] compared with the homozygous normal or heterozygous genotypes. Overall, we observed a marginal significant increased risk of colorectal cancer (OR, 1.78; 95% CI, 0.93-3.42) among those whose plasma folate levels indicated deficiency (<3 ng/ml) compared with men with adequate folate levels. Among men with adequate folate levels, we observed a 3-fold decrease in risk (OR, 0.32; 95% CI, 0.15-0.68) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes. However, the protection due to the mutation was absent in men with folate deficiency. In men with the homozygous normal genotype who drank little or no alcohol as reference, those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk (OR, 0.12; 95% CI, 0.03-0.57), and for moderate drinkers, a 2-fold decrease in risk (OR, 0.42; 95% CI, 0.15-1.20); no decrease in risk was seen in those drinking 1 or more drinks/day. Our findings provide support for an important role of folate metabolism in colon carcinogenesis. In particular, these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk, perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis, but that low folate intake or high alcohol consumption may negate some of the protective effect.
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PMID:Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. 906 78

The prospect that high intake of certain vitamins may confer protection against cancer has drawn substantial attention during the last decades. This paper gives a concise update of the role of a number of promising vitamins in prevention of cancer. Vitamin A and its analogues have an important role in cellular processes related to carcinogenesis. However, blood vitamin A levels are under strict control and a high intake of preformed vitamin A does not seem to be relevant for cancer prevention. The antioxidant vitamins C and E and beta-carotene may also have other biological activities than free radical trapping that relate to their cancer preventive properties. Mechanisms include immune stimulation, inhibition of nitrosamine formation, enhancement of cell communication and an influence on metabolic activation of carcinogens. Epidemiological data for the antioxidant vitamins are promising, but cannot rule out that another factor or combination of factors in fruits and vegetables might be responsible for a protective effect. The B vitamin folic acid is one of these potential factors that is currently thought to have an influence on DNA methylation and thus on proto-oncogene expression. Folic acid seems to be promising and deserves further study. Vitamin D might be relevant in colon cancer development due to its close links with calcium metabolism that might influence cell proliferation. Overall, results are promising, but the first human intervention trials on (antioxidant) vitamins and human cancer have yielded somewhat disappointing results. At this moment the data seem insufficient to make recommendations for vitamin supplementation to prevent cancer. The results are certainly in line with the advice that a diet rich in fruits and vegetables will help reduce cancer risk.
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PMID:Vitamins and cancer. 910 91

Folic acid supplementation may help prevent the following three common and important disorders: neural tube defect pregnancies, ischemic heart disease and strokes, and possibly colon cancer. Several studies have irrefutably established that folic acid supplementation in proper doses reduces neural tube defect pregnancies. Fortified food would be the most reliable way to address this health issue. Several epidemiologic reports have established a close link between hyperhomocysteinemia and ischemic heart disease. This is supported by evidence obtained from genetic defects leading to elevated plasma levels of homocysteine. There is reasonable evidence to conclude that hyperhomocysteinemia is the actual cause of excessive cardiac diseases. Again, folic acid supplementation in proper doses could potentially reduce ischemic heart disease by 40% There is also some evidence to suggest that folic acid treatment reduces the incidence of colon cancer. The reduction in all three health problems is dependent upon the dose of folic acid administered. The levels needed are rarely supplied by the daily food intake, even under ideal conditions, although breakfast cereals address this problem at least in part. It is proposed that flour be fortified because it is a food product heavily used by most people, and that governmental agencies should oversee such programs because they are responsible for setting public health policies.
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PMID:Fortifying food with folic acid. 1101 53

Folate status is inversely related to the risk of colorectal cancer. Whether conventional blood measurements of folate status accurately reflect folate concentrations in the colorectal mucosa has been a controversial topic. This is an important issue because accurate measures of folate status in the colorectal mucosa are important for ascertaining the risk of colorectal cancer in epidemiological studies and for determining the effects of folate supplementation in clinical trials. We examined whether conventional blood measurements of folate and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflect folate concentrations in human colonic mucosa obtained by endoscopic biopsy. Study subjects (n = 20) were participants in a randomized trial that investigated the effect of folate supplementation (5 mg daily for 1 year) on provisional molecular markers of colon cancer. Blood samples and biopsies of normal rectosigmoid mucosa were obtained at baseline, at 6 months, and at 1 year. Serum, RBC, and colonic mucosal folate and serum homocysteine concentrations were determined. Colonic mucosal folate concentrations correlated directly with serum folate concentrators at each time point (r = 0.572-0.845; P < 0.015) and with RBC folate concentrations at 6 months and 1 year (r = 0.747-0.771; P < 0.001). Colonic mucosal folate concentrations correlated inversely with serum homocysteine concentrations at each time point (r = -0.622-0.666; P < 0.008). Systemic measures of folate status did not correlate with colonic mucosal folate concentrations among individuals receiving supplemental folate. Our observations indicate that colonic mucosal concentrations of folate may be predicted accurately by blood measurements of folate status only among individuals not ingesting supraphysiological quantities of folate.
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PMID:Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate status among individuals ingesting physiologic quantities of folate. 1140 25

Folate is involved in the synthesis of nucleotides and amino acid metabolism such as methylation of homocysteine to methionine. Methionine is activated by adenosine triphosphate (ATP) to produce S-adenosylmethionine (SAM), the primary intracellular methyl donor. Thus, folate is essential for the synthesis, methylation, and repair of DNA. With regard to its biochemical function it has been hypothesized that a diminished folate status may contribute to carcinogenesis by alteration of gene expression and increased DNA damage. Animal and human studies support this hypothesis, particularly with respect to colorectal cancer. Epidemiological evidence for the association between folate status and cancer was first observed among ulcerative colitis patients. Several case-control studies demonstrated reduction in colorectal cancer risk with better folate status. Two large, prospective cohort studies support the concept that high folate intake is protective against colon cancer. In contrast to colorectal cancer, the potential association of folate status and risk has been less investigated in breast cancer. Recently, convincing epidemiological data establishing a positive effect of folate status on breast cancer risk were published. This review summarizes the epidemiological evidence for the association between folate status and colorectal and breast cancer risk. In addition, a short overview is given on the discussed mechanism(s) by which folate might be involved in carcinogenesis.
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PMID:Beneficial role for folate in the prevention of colorectal and breast cancer. 1169 47

Many epidemiologic, animal and human studies suggest that folate status modulates carcinogenesis. Although these observations have been made in a number of tissues, the data are clearly most compelling for the colorectum. The mechanism(s) by which this modulation is mediated remains ill defined. Alterations in either genome-wide or gene-specific DNA methylation and/or alterations in DNA stability, resulting from DNA strand breaks or uracil misincorporation, are leading candidates in this regard. Folate has a central role in biological methylation and nucleotide synthesis, and therefore it is not surprising that folate depletion has been observed to alter DNA methylation and diminish DNA stability. The hypothesis that these two pathways are the means by which folate modulates cancer risk is also supported by the epidemiological observation that a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) gene differentially affects the relative risk of colon cancer depending on folate status, because MTHFR catalyzes the reaction that determines whether cellular folate is diverted into biological methylation or nucleotide synthesis. This phenomenon suggests that it is an imbalance between biological methylation and nucleotide synthesis that is responsible for folate-related carcinogenesis. The control of cell proliferation, which also is related to DNA methylation, is another candidate mechanism by which folate status modulates carcinogenesis. In cell culture studies, folate supplementation has been observed to suppress excessive cell proliferation. Understanding the mechanisms by which folate status modulates carcinogenesis is important for advancing insight into cancer biology and for facilitating those efforts to translate research in folate and carcinogenesis into effective and safe public health initiatives.
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PMID:Folate status: effects on pathways of colorectal carcinogenesis. 1216 3

Although many mechanisms remain unclear, a large body of evidence indicates that several dietary and lifestyle factors are likely to have a major influence on the risk of colon cancer. Physical inactivity, excess body weight, and a central deposition of adiposity are consistent risk factors. Overconsumption of energy is likely to be one of the major contributors to the high rates of colon cancer in Western countries. Beyond their influence on energy balance, the independent role of specific macronutrients remain controversial. Red meat, processed meats, and perhaps refined carbohydrates contribute to risk. Recent evidence indicate that chronic hyperinsulinemia may increase risk of colon cancer. As insulin resistance and subsequent hyperinsulinemia is induced by excess energy intake and some aspects of the Western diet (e.g., saturated fats and refined carbohydrates), insulin may be a focus of factors influencing colon cancer risk. Recent evidence also points to a role of IGF-1, but our understanding of modifiable factors that influence levels of these is poor at present. Of note is that hyperinsulinemia increases free IGF-1 exposure [25]. High alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, and smoking early in life are likely to increase risk of colon cancer. Recent epidemiologic studies have tended not to support a strong influence of fiber; instead, some micronutrients or phytochemicals in fiber-rich foods may be important. Folate is one such nutrient that has received attention lately and is being studied in randomized intervention trials. Agents with chemopreventive properties, such as aspirin and postmenopausal estrogens, have potential adverse effects so a careful consideration of the risk-benefit ratio is required before general recommendations can be made. Other NSAIDs with a potential for reduced toxicity, such as celecoxib, are currently being evaluated for efficacy and toxicity. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. At least 70% of colon cancers may be preventable by moderate changes in diet and lifestyle [197]. Secondary prevention, through screening by sigmoidoscopy and colonoscopy, is also critically important to prevent mortality from colon cancer; however, many of the diet and lifestyle risk factors for colon cancers are the same for cardiovascular disease and for some other cancers, so focusing on the modifiable risk factors for colon cancer is likely to have many additional benefits beyond this cancer.
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PMID:Modifiable risk factors for colon cancer. 1248 70

Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.
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PMID:Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. 1273 16

African Americans have the highest incidence of colon cancer among United States racial/ethnic groups, but these disparities are largely unexplained. This report describes associations of micronutrients with colon cancer risk in African Americans and whites using data from a case-control study in North Carolina. Incident cases of histologically confirmed colon cancer, age 40-80 years (n = 613), and matched controls (n = 996) were interviewed in person to elicit information on potential colon cancer risk factors. A previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year prior to diagnosis or interview date. Micronutrient exposure included food sources and dietary supplements. Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (ORs). African Americans reported lower mean micronutrient intakes than whites, primarily due to larger contributions from dietary supplements in whites. Controls generally reported higher micronutrient intakes than cases; however, these differences were only statistically significant for whites. In whites, high beta-carotene, vitamin C, and calcium intakes were associated with 40-60% reductions in colon cancer risk when contrasting highest to lowest quartiles in both energy-adjusted and non-energy-adjusted models, e.g., OR = 0.4 (95% confidence interval, 0.3-0.6) for the highest quartile of calcium in the energy-adjusted model. In African Americans, vitamins C and E were strongly inversely associated using both statistical approaches: high vitamin E intake was associated with a 70% reduced risk for colon cancer, and the OR comparing the highest to lowest quartiles of vitamin C was 0.5 (95% confidence interval, 0.3-0.8). Folate and lutein were not statistically significantly associated with colon cancer risk in either racial group. These results suggest that at high intakes, micronutrients commonly found in plant and other foods (in particular, beta-carotene, vitamin C, and calcium in whites and vitamins C and E in African Americans) exhibit independent associations consistent with 30-70% reductions in colon cancer risk.
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PMID:Associations of micronutrients with colon cancer risk in African Americans and whites: results from the North Carolina Colon Cancer Study. 1506 39


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