Colorectal cancer vitamin

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 view of the reported growing importance ascribed to folic acid deficiency in the prevention of various disease conditions, such as neural tube defects, megaloblastic anemia, colon cancer, and colorectal cancer, a dissolution requirement is specified for folic acid when it is present in multivitamin-mineral combination products. Currently, the dissolution standard required in the official articles of dietary supplements (including vitamin-mineral combination products) places folic acid outside the index vitamin hierarchy. Therefore, a mandatory dissolution test for folic acid is required that is independent of and in addition to the mandatory index vitamin test for multivitamin preparations containing folic acid. 

Martinez, M. E., and Willett, W. C. (1998). Calcium, vitamin D, and colorectal cancer A review of the epidemiologic evidence. Cancer Epidemiol. Biomarkers Prev. 7,163-168. 

Garland, C., Barrett-Connor, E., Rossof, A. H., Shekelle, R. B., Criqui, M. H. and Paul, O. 1985. Dietary vitamin D and calcium and risk of colorectal cancer A 19-year prospective study in men. Lancet 1, 307-309. 

In the study on colorectal cancer (Table 20.4), a reduced risk was found for increasing intake of anthocyanidins (OR, 0.67 for the highest versus the lowest quintile,p-trend, 0.001), flavonols (OR, 0.64,p-trend < 0.001), flavones (OR, 0.78, p-trend, 0.004), and isoflavones (OR, 0.76, p-trend, 0.001). [Rossi et al., 2006], The estimates did not substantially differ for colon and rectal cancers. After allowance for fruit and vegetable consumption, for dietary fiber, or for micronutrients previously associated to this tumor including vitamin C, the associations with flavonoids did not change by more than 10%. A recent case-control study of 1456 pairs of cases and controls conducted in Sweden confirmed a significant decrease in risk of colorectal cancer for intake of anthocyanidins and flavonols [Theodoratou et al., 2007], but there was no relation for isoflavones and flavones. However, the results on isoflavones and flavones are questionable due to the unusually and generally low intakes of the populations studied. In the Italian population, anthocyanidins were derived mainly from wine, red fruit, and onions, and flavonols from apples or pears, wine, and mixed salads. 

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.)... 

Although fruit and, more consistently, vegetable intakes are inversely associated with colorectal cancer risk, the epidemiological evidence for vitamin C as a specific protective factor is less consistent. Since 1990, two out of four prospective studies have observed a significant inverse association between vitamin C intake and the risk of colon or rectal cancer. In a prospective cohort study that followed 4277 elderly men and 7300 elderly women over 8 years, women who consumed more than 225mg/d of vitamin C had a 39% lower risk of colon cancer than women who consumed less than 155mg/d, but no association between vitamin C intake and colon cancer risk was observed for men. A similar decrease in colon cancer risk was observed in women who took vitamin C supplements. A recent study of colon cancer mortality in more than 700,000 U.S. men and women found that the use of vitamin C supplements for at least 10 years was associated with a 60% reduction in rectal cancer risk, but was not significantly associated with colon cancer risk. ... 

Neither dietary nor serum p-carotene levels have been significantly inversely associated with colorectal cancer risk, " and only one out of seven prospective studies observed a significant inverse association between measures of vitamin E intake... 

Several small intervention trials have used indices of colorectal epithelial cell proliferation as intermediate endpoints. Supplementation with 3g/d of vitamin C for at least 18 months resulted in a significantly decreased proliferation index in rectal epithehal cells compared with placebo in patients with FAP " " In another small trial, supplementation with 750mg/d of vitamin C or 9mg/d of p-carotene but not 160mg/d of vitamin E for one month decreased cell proliferation in colonic crypts of adenoma patients compared with the baseline. However, supplementation of colorectal adenoma or colorectal cancer patients with 30mg/d of p-carotene for 3 months decreased indices of colonic cell proliferation when compared with a placebo. A stndy of colon cancer patients randomized to receive a combination of lOOOmg/d of vitamin C, 70mg/d of a-tocopherol, 30,000 lU/d of vitamin A, and 2000mg/d of calcinm or placebo for 6 months... 

Jacobs, E.J., Connell, C.J., Patel, A.V., Chao, A., Rodriguez, C., Seymour, J., McCullough, M.L., Calle, E.E., and Thun, M.J., Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort. Cancer Epidemiol Biomarkers... 

B., Svanoni, F., Giro la, M. et al.. Colorectal Cancer Study Group of the University of Modena and the Elealth Care District 16 Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas, Dis. Colon Rectum, 36, 227, 1993. 

In an open study, 4 patients with breast or colorectal cancer received a single 20-mg dose of warfarin 8 days before starting oral capecitabine (3 cycles of capecitabine 1250 mg/w twice daily for 14 days, then 7 days rest), then again on day 12 of the third cycle of capecitabine. Capecitabine increased the AUC of 5-warfarin was increased by 57%, and its elimination half-life by 51%, without any significant changes to A-warfarin. The maximum INR was increased by 1.9-fold and the AUC of the INR increased 2.8-fold. Three of the patients required vitamin K administration. Because of the clear, statistically significant findings in these 4 patients, the study was terminated early. ... 

This study, described as a randomized double-blind comparison of vitamin C (10 g per day) and a lactose placebo in 100 patients with advanced adenomatous colorectal cancer, gave survival times published only in a Kaplan-Meier figure. We have measured the published curves and produced the semilogarithmic plot shown as Fig. 4. 

Fig. 4. Logarithm of the Kaplan-Meier survival percentage S for advanced colorectal cancer patients for two cohorts (vitamin C and placebo) as a function of the time f from onset of treatment (data from ref. 6).

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 dietary intake of vitamin Bg and cancer has been extensively investigated for colorectal cancer in prospective studies. Results from a meta-analysis of nine prospective studies indicated that there is no significant association between vitamin Bg intake and colorectal cancer risk (Larsson et al. 2010) (Figure 42.4). For some groups such as those who drink alcohol, however, possible beneficial effect of vitamin Bg has been observed (Ishihara et al. 2007) (Figure 42.5). Regarding case-control studies, in contrast, a meta-analysis of six studies indicated a significant association between vitamin Bg intake and colorectal cancer (Theodoratou et al. 2008). 

Figure 42.4 Adjusted relative risks of colorectal cancer for the highest vs. lowest categories of vitamin Be intake or blood PLP level. Source Larsson et al. (2010), cited with permission of The Journal of the American Medical Association. The size of each square is proportional to the study s weight (inverse of variance). "The range is the dilference in the midpoint between the highest and lowest categories of exposure. Exclusion of the study by de Vogel et al. which appeared to explain the study heterogeneity, yielded a pooled relative risk of 0.80 (95% Cl, 0.69-0.92) with no heterogeneity among studies (P = 0.23 12 = 24% 95% Cl, 0- %).

Figure 42.5 Hazard ratio of colorectal cancer according to quartiles of vitamin 85 intake by alcohol intake among men. Results from a prospective cohort study indicated that higher intake of vitamin Bg may be beneficial in men with higher alcohol intake. The risk of colorectal cancer associated with alcohol intake was significantly higher in those who had the lowest level of vitamin 85 intake, but the risk decreased in those with higher vitamin Bg intake. Statistically significant.

The association between blood level of vitamin Bg and colorectal cancer has been prospectively investigated in nested case-control studies. Findings from a meta-analysis of four nested case-control studies indicated a reduced risk of colorectal cancer with an increased blood PLP level (Larsson et al. 2010), with the dose-response analysis indicating a 49% decrease in risk for every lOOpmol/mL increase in blood PLP level. Results from a subsequent nested case-control study published after the meta-analysis also indicated an inverse association between the sum of vitamin Bg species (PLP, PL, PA), in addition to PLP and PL alone, with colorectal cancer (Eussen et al. 2010a). This study also found that the inverse association was stronger among males who drank > 30 g of alcohol a day (Eussen et al. 2010a). 

Recent evidence from observational studies indicates a possible association between vitamin Bg status and cancer, particularly colorectal cancer, albeit that the results from trials are still limited. 

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-... 

Ishihara, J., Otani, T., Inoue, M., Iwasaki, M., Sasazuki, S., and Tsugane, S. for the JPHC Study Group, (2007). Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. The Journal of Nutrition. 137 1808-1814. 

Larsson S.C., Giovannucci E., and Wolk A., 2005. Vitamin B6 intake, alcohol consumption, and colorectal cancer a longitudinal population-based cohort of women. Gastroenterology. 128 1830-1837. 

Larsson, S.C., Orsini, N., and Wolk, A., 2010. Vitamin B6 and risk of colorectal cancer a meta-analysis of prospective studies. The Journal of the American Medical Association. 303 1077-1083. 

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