Folate colorectal cancer

The risk of colon cancer appears to be inversely related to calcium and folate intake. Calciums protective effect may be related to a reduction in mucosal cell proliferation rates or through its binding to bile salts in the intestine, whereas dietary folate helps in maintaining normal bowel mucosa. Additional micronutrient deficiencies have been demonstrated through several studies to increase colorectal cancer risk and include selenium, vitamin C, vitamin D, vitamin E, and 3-carotene however, the benefit of dietary supplementation does not appear to be substantial.11... 

In chapter 3, we briefly discussed the link between elevated homocysteine levels, increased acidity, and, ultimately, cardiovascular problems. While additional studies are required, promising scientific evidence suggests that folate (also known as vitamin Bg), vitamin B6, and vitamin BI2 are effective at lowering homocysteine levels and may ultimately play a role in reducing vascular disease. In addition, research has revealed an inverse relationship between folate and the occurrence of colorectal cancer.5 (In other words, the more deficient in folate you are, the greater your risk of colorectal cancer.)... 

The classic antifolate methotrexate MTX continues to be an important component of the chemotherapeutic armamentarium for a variety of cancers including pediatric ALL, osteogenic sarcoma, lymphoma, and breast cancer. Raltitrexed, another anti-folate, is used throughout much of the world outside of the United States for advanced colorectal cancer. Finally, Peme-trexed was approved in 2004 for the treatment of pleural mesothelioma and shortly thereafter as a second line treatment for nonsmall cell lung cancer. These drugs mimic the natural folate molecule and in so doing utilize the membrane-bound reduced folate carrier (RFC) protein system to gain entry into the cell. 

Engeland, M. et al., Effects of dietary folate and alcohol intake on promoter methylation in sporadic colorectal cancer The Netherlands Cohort Study on Diet and Cancer, Cancer Res., 63, 3133-3137, 2003. 

Folates Folates are foUc acid derivatives that are naturally present in foods. FoUc acid is the chemically synthesized form of folate. Folates are involved in many metaboUc pathways such as DNA and RNA biosynthesis, repair and methylation, and amino acid interconversions. These compounds possess antioxidant competence that protects the genome by preventing free radical attack [238]. In humans, folate deficiency is associated with a variety of disorders such as coronary heart disease, osteoporosis, Alzheimer s disease, and increased risk of breast and colorectal cancer [239]. 

B vitamin intake or vitamin blood concentrations have also been related to various cancers. The cancer types that have been best investigated with respeet to folic acid are colon cancer and colorectal cancer. Convincing evidence from observational studies led to the initiation of randomized controlled trials with folic acid in colorectal adenomas. However, similar to cardiovascular disease, there seems to be a discrepancy between the observational epidemiological studies that reported in the majority an inverse association of folate and cancer risk, and the effect of folic acid supplementation in the randomized controlled trials, which reported no effect of folic add on recurrence of colorectal adenoma risk. 

The association between folate intake and colorectal cancer in 27 observational epidemiological studies was analysed in a recent meta-analysis (Keimedy et al. 2011). This meta-analysis, which included 18 case-control studies and nine cohort studies, showed that high folate intake was associated with reduced risk of colorectal adenomas. The association was stronger in case-control studies [relative risk (RR) 0.85 95% confidence interval (Cl) 0.74-0.99] than in cohort studies (RR 0.92 95% Cl 0.81-1.05). 

Colorectal cancer Folate/folic acid Methylation RCTs with folic acid did not show reduced risk of recurrence Figueiredo et al. (2011)... 

Kennedy, D.A., Stern, S.J., Moretti, M., Matok, I., Sarkar, M., Nickel, C., and Koren, G., 2011. Folate intake and the risk of colorectal cancer a systematic review and meta-analysis. Cancer Epidemiology. 35 2-10. 

Moreover, the correlation between folate intake and the occurrence of pregnancy neural tube defects has been previously studied and extensively discussed (Hibbard 1964 Mulinare et al. 1988). Based on the study by Johnson and Lund (2007), folate intake was also found to be inversely related to the risk of colorectal cancer. 

Harnack L., Jacobs D.R. Jr, Nicodemus K., Lazovich D., Anderson K., and Folsom A.R., 2002. Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. Nutr Cancer. 43 152-... 

Shrubsole, M.J., Yang, G., and Gao, Y.T., et al., 2009. Dietary B vitamin and methionine intakes and plasma folate are not associated with colorectal cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev. 18 1003-1006. 

Kim, Y.I., 2006. Folate a magic bullet or a double edged sword for colorectal cancer prevention Gut. 55 1387-1389. 

While observational studies had reported inverse associations of dietary intake of folate (or blood levels of folate) with overall risks of cancer, colorectal cancer or breast cancer (Giovannucci et al. 2002 Larsson et al. 2007 Lin et al. 2008 Zhang et al. 2003), one small trial involving 1021 individuals with a prior history of colorectal adenoma suggested a possible adverse effect on both the risk of recurrent colorectal adenoma (Cole et al. 2007) and on prostate cancer... 

Tumours The association between intakes of folate, vitamin Bs and vitamin B12 and the risk of colorectal cancer in women has been examined. Food fortification with folic acid for 3-9 years was associated with an increased risk... 

International recommendation tables are constantly subject to review, particularly in view of the relationship between folate status and the risk of NTD and specific chronic diseases including coronary artery disease and colorectal cancer. 

E. Giovannucci et al., Folate, Methionine, and Alcohol Intake and Risk of Colorectal Adenoma, J. Natl. Cancer Inst. 85 (1993) 875-84. 

Although folate is widely distributed in foods, dietary deficiency is not uncommon, and a number of commonly used drugs can cause folate depletion. Marginal folate status is a factor in the development of neural tube defects and supplements of 400 fj,g per day periconceptually reduce the incidence of neural tube defects significantly. High intakes of folate lower the plasma concentration of homocysteine in people genetically at risk of hyperhomo-cysteinemia and may reduce the risk of cardiovascular disease, although as yet there is no evidence from intervention studies. There is also evidence that low folate status is associated with increased risk of colorectal and other cancers and that folate may be protective. Mandatory enrichment of cereal products with folic acid has been introduced in the United States and other countries, and considered in others. 

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