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Cancers
BACKGROUND: Mounting evidence suggests that a low intake of the water-soluble B vitamin folate is associated with breast and colorectal carcinogenesis, especially among alcohol drinkers. However, epidemiologic data specifically linking folate intake to ovarian cancer risk are limited. METHODS: We examined the association between dietary folate intake (i.e., folate from food sources) and the incidence of total epithelial ovarian cancer and its subtypes by analyzing data from the Swedish Mammography Cohort, a population-based prospective cohort of 61 084 women, aged 38-76 years, who, at baseline (i.e., from 1987 to 1990), were cancer-free and had completed a food-frequency questionnaire. Through June 30, 2003, 266 incident cases of invasive epithelial ovarian cancer were diagnosed. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of ovarian cancer with 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Overall, dietary folate intake was weakly inversely associated with total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake = 0.67, 95% CI = 0.43 to 1.04; P(trend) =.08). Among women who consumed more than 20 g of alcohol (approximately two drinks) per week, there was a strong inverse association between dietary folate intake and total epithelial ovarian cancer risk (RR for highest versus lowest quartile of intake = 0.26, 95% CI = 0.11 to 0.60; P(trend) =.001), but among women who consumed 20 g or less of alcohol per week, there was no such association (RR for highest versus lowest quartile of intake = 1.00, 95% CI = 0.59 to 1.70; P(trend) =.80). The absolute risk of epithelial ovarian cancer for the lowest three quartiles versus the highest quartile of folate intake was 8 per 100 000 person-years (95% CI = 0 to 16 per 100 000 person-years) overall and 26 per 100 000 person-years (95% CI = 10 to 42 per 100 000 person-years) among those who consumed more than 20 g of alcohol per week. The association between dietary folate intake and cancer risk did not vary substantially among subtypes of epithelial ovarian cancer. CONCLUSION: A high dietary folate intake may play a role in reducing the risk of ovarian cancer, especially among women who consume alcohol. Boutron-Ruault, Senesse, Faivre Epidemiologic studies have suggested that high alcohol and low folate intakes might be jointly associated with colorectal tumors via DNA metabolism. We investigated this hypothesis in a case-control study comparing small adenoma (< 10 mm, n = 154), large adenoma (n = 208), and polyp-free (n = 426) subjects, recruited after colonoscopy, and cancer cases (n = 171) with population controls (n = 309). Odds ratios for the fifth vs. the first quintile of intake (OR5) were as follows: Folate intake was related to the risk of small and large adenomas compared with polyp-free subjects [OR5 = 0.5, 95% confidence interval (CI) 0.3-1.0; OR5 = 0.5, 95% CI 0.3-1.0, respectively], whereas alcohol was related to risk of large adenomas (OR5 = 4.1, 95% CI 2.1-8.1), but not of small adenomas (OR5 = 1.2, 95% CI 0.7-2.2). In large adenomas, there was some interaction between alcohol and folate, with a stronger protective effect of folate with high alcohol intake and a stronger risk with alcohol with low folate intake. For cancer patients compared with general population controls, neither alcohol (OR5 = 1.6, 95% CI 0.8-3.0) nor folates (OR5 = 1.0, 95% CI 0.5-2.0) were related to risk. Our data support the hypothesis that folate intake might be mostly beneficial to prevent adenoma formation but might have an additional protective effect against adenoma growth associated with alcohol.
BACKGROUND: Reduced methylation of DNA may contribute to loss of the normal controls on proto-oncogene expression. In humans, hypomethylation of DNA has been observed in colorectal cancers and in their adenomatous polyp precursors. Accumulation of DNA methylation abnormalities, observed during progression of human colorectal neoplasia, may be influenced by certain dietary factors. The apparent protective effect of fresh fruits and vegetables, the major folate sources, on colorectal cancer incidence suggests that a methyl-deficient diet contributes to occurrence of this malignancy. Low dietary folate and methionine and high intake of alcohol may reduce levels of S-adenosylmethionine, which is required for DNA methylation. PURPOSE: To determine if dietary factors that may influence methyl availability are related to colorectal adenomas, we prospectively examined the association of folate, methionine, and alcohol intakes and risk of colorectal adenoma. METHODS: We assessed dietary intake for a 1-year period for women of the Nurses' Health Study, started in 1976, and for men of the Health Professionals Follow-up Study, started in 1986--using a semiquantitative food frequency questionnaire. Adenomatous polyps of the left colon or rectum were diagnosed in 564 of 15,984 women who had had an endoscopy between 1980 and 1990 and in 331 of 9490 men who had undergone an endoscopy between 1986 and 1990. RESULTS: High dietary folate was inversely associated with risk of colorectal adenoma in women (multivariate relative risk [RR] = 0.66; 95% confidence interval [CI] = 0.46-0.95 between high and low quintiles of intake) and in men (RR = 0.63; 95% CI = 0.41-0.98) after adjusting for age, family history, indications for endoscopy, history of previous endoscopy, total energy intake, saturated fat intake, dietary fiber, and body mass index. Relative to nondrinkers, drinkers of more than 30 g of alcohol daily (about two drinks) had an elevated risk of adenoma (in women, RR = 1.84, 95% CI = 1.19-2.86; in men, RR = 1.64, 95% CI = 0.92-2.93). Methionine intake was inversely associated with risk of adenomas 1 cm or larger (RR = 0.62; 95% CI = 0.46-0.85, combining men and women). CONCLUSIONS: Folate, alcohol, and methionine could influence methyl group availability, and a methyl-deficient diet may be linked to early stages of colorectal neoplasia. A dietary pattern that increases methyl availability could reduce incidence of colorectal cancer. IMPLICATIONS: These data support efforts to increase dietary folate in segments of the population having diets with low intakes of this nutrient. Giovannucci, Stampfer, Colditz OBJECTIVE: To evaluate the relation between folate intake and incidence of colon cancer. DESIGN: Prospective cohort study. SETTING: 88,756 women from the Nurses' Health Study who were free of cancer in 1980 and provided updated assessments of diet, including multivitamin supplement use, from 1980 to 1994. PATIENTS: 442 women with new cases of colon cancer. MEASUREMENTS: Multivariate relative risk (RR) and 95% CIs for colon cancer in relation to energy-adjusted folate intake. RESULTS: Higher energy-adjusted folate intake in 1980 was related to a lower risk for colon cancer (RR, 0.69 [95% CI, 0.52 to 0.93] for intake > 400 microg/d compared with intake < or = 200 microg/d) after controlling for age; family history of colorectal cancer; aspirin use; smoking; body mass; physical activity; and intakes of red meat, alcohol, methionine, and fiber. When intake of vitamins A, C, D, and E and intake of calcium were also controlled for, results were similar. Women who used multivitamins containing folic acid had no benefit with respect to colon cancer after 4 years of use (RR, 1.02) and had only nonsignificant risk reductions after 5 to 9 (RR, 0.83) or 10 to 14 years of use (RR, 0.80). After 15 years of use, however, risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]), representing 15 instead of 68 new cases of colon cancer per 10,000 women 55 to 69 years of age. Folate from dietary sources alone was related to a modest reduction in risk for colon cancer, and the benefit of long-term multivitamin use was present across all levels of dietary intakes. CONCLUSIONS: Long-term use of multivitamins may substantially reduce risk for colon cancer. This effect may be related to the folic acid contained in multivitamins.
Hematologic studies, including serum and RBC folate assays, were done on 45 outpatients with chronic colitis who either took sulfasalazine (n = 27) or did not use it (n = 18). Overall, sulfasalazine users and nonusers had similar mean hemoglobin, hematocrit, serum folate, and RBC folate levels. However, within the drug users, RBC folate was inversely correlated with drug dose; serum folate was not. Patients taking 2 g or more of sulfasalazine daily had lower mean RBC folate levels (221.2 +/- 27.3 ng/mL) than patients either taking less (371.7 +/- 35.0 ng/mL) or nonusers (330.3 +/- 30.3 ng/mL). Mean corpuscular volume was also related to drug dose but not to RBC folate. Although maintenance sulfasalazine use rarely causes clinically significant folate deficiency, subclinical tissue depletion occurs as a dose-related effect. Lashner, Provencher, Seidner, Knesebeck, Brzezinski BACKGROUND & AIMS: Two case-control studies have shown that folate may protect against neoplasia in ulcerative colitis. This historical cohort study was performed to better define this association. METHODS: The records of 98 patients with ulcerative colitis who had disease proximal to the splenic flexure for at least 8 years were reviewed. Documented folate use of at least 6 months was deemed a positive exposure. RESULTS: Of the patients, 29.6% developed neoplasia and 40.2% took folate supplements. The adjusted relative risk (RR) of neoplasia for patients taking folate was 0.72 (95% confidence interval [CI], 0.28-1.83). The dose of folate varied with the risk of neoplasia (RR, 0.54 for 1.0 mg folate; RR, 0.76 for 0.4 mg folate in a multivitamin compared with patients taking no folate). Folate use also varied with the degree of dysplasia (RR for cancer, 0.45; RR for high-grade dysplasia, 0.52; RR for low-grade dysplasia, 0.75 compared with patients with no dysplasia) (P = 0.08). CONCLUSIONS: Although not statistically significant, the RR for folate supplementation on the risk of neoplasia is < 1 and shows a dose-response effect, consistent with previous studies. Daily folate supplementation may protect against the development of neoplasia in ulcerative colitis.
We have evaluated the effect of folate supplementation (5 mg/day) on global deoxyribonucleic acid (DNA) methylation status of the rectal mucosa of 20 patients with resected colonic adenomas in a prospective, controlled, cross-over study. Baseline values of DNA methylation were inversely correlated with caloric (P = 0.03) and fat intake (P = 0.05) and patients harbouring multiple polyps consumed significantly more calories (P = 0.0006), fat (P = 0.009) and carbohydrates (P = 0.009) as compared to patients having one single lesion. Folate supplementation resulted in a significant decrease of DNA hypomethylation in 7/20 patients (P = 0.05) which returned to previous values after placebo treatment. This effect was significantly correlated with number of polyps, with all the responders presenting one single lesion, whereas 8/13 of the non-responders had multiple ones (chi2 = 7.17, P = 0.007). In conclusion, folate supplementation may decrease degree of DNA hypomethylation, but only in patients with one single polyp. In those with multiple lesions, other nutritional factors such as caloric and fat intake, may be more determinant. Diculescu, Ciocîrlan, Ciocîrlan, Pi?igoi, Becheanu,
Croitoru, Spanache BACKGROUND: The purpose of the study was to assess whether folic acid supplementation and long term therapy with sulfasalazine can reduce the risk of colorectal cancer (CRC) development in longstanding extensive ulcerative colitis. MATERIAL AND METHODS: A meta-analysis was performed including the last 10 years published and Medline indexed studies on this subject. RESULTS: 3 studies have been included concerning the protective effect of folate supplementation in development of CRC. The association of these two factors is significant (effect size r =0.124, p = 0.025). The fail-safe number of studies with an opposite result should be 4 to revert the significance. 4 studies regarding sulfasalazine's protective effect in longstanding extensive ulcerative colitis have also been evaluated. A similar significance has been obtained, r = 0.148, p = 0.0007 and a fail-safe number of studies equal to 7. The homogeneity of these studies is validated by standard tests. CONCLUSIONS: Both sulfasalazine therapy and folate supplementation have a protective effect in colorectal cancer development in a population of patients with longstanding ulcerative colitis. Randomized controlled trials are needed to explore these hypotheses.
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