Serum folate, homocysteine and colorectal cancer risk in women: a nested case–control study

Abstract

Summary Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with belowmedian serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials.

Folate fortification, plasma folate, homocysteine and colorectal adenoma recurrence

“…3,4 Data from the present analyses show that higher homocysteine is a significant risk factor for adenoma recurrence among nonusers of multivitamins. This suggests that despite folate fortification, variation remains in homocysteine that predicts adenoma risk.…”

“…A recent meta analysis showed a significant 20-25% lower risk of developing colorectal cancer among individuals in the highest compared to those in the lowest category of dietary folate 1 ; inverse associations between blood folate and colorectal neoplasia (i.e., cancer and adenoma) have also been shown. [2][3][4] Mechanisms responsible for the inverse association of folate on risk of colorectal cancer are not entirely understood and may involve disturbances in DNA synthesis, methylation and repair, 5-7 albeit alternate mechanisms have been proposed. 8 Homocysteine, a biochemical marker of folate status, is an amino acid that is metabolized via remethylation into methionine, facilitated by folic acid and vitamin B 12 or trans-sulfuration to cysteine, facilitated by vitamin B 6 .…”

“…9 Few data exist on the relation between homocysteine and colorectal neoplasia. 3,4 In 1996, the United States Food and Drug Administration (FDA) issued a regulation for the prevention of neural tube defects (NTDs), requiring that all enriched cereal grain products (i.e., flour, rice, pasta, breads, etc.) be fortified 11 with 140 lg of folic acid/100 g, which would provide an estimated additional 80-100 lg/day to women of childbearing age and 70-120 lg to middle-aged and older adults.…”

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

“…Furthermore, low serum (Bird et al, 1995;Kato et al, 1999) and erythrocyte folate concentrations (Lashner, 1993;Bird et al, 1995;Paspatis et al, 1995) have been reported to be associated with the development of adenoma or cancer.…”

Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

“…Low folate from diet or in circulation has been associated with increased risk of colorectal cancer in several prospective studies (Giovannucci et al, 1995;Kato et al, 1999) In a cohort of 505 Chinese from Singapore, Trinh et al (2002) found that TS 3R/3R genotype was associated with reduced plasma folate and, among individuals with low dietary folate intake, with elevated plasma homocysteine levels. These results suggest that TS and methylenetetrahydrofolate reductase compete for limiting supplies of folate required for the remethylation of homocysteine.…”