Nutrient Shows Colorectal Polyp Risk

BOSTON, Aug. 7 -- The nutrient choline appears to increase colorectal polyp risk rather than being a chemopreventive agent as was expected, researchers here found.
In an analysis of a large epidemiological study, colorectal adenoma risk was 45% higher for women who had the highest choline intake than for those with the lowest intake (95% confidence interval 27% to 67%, P<0.001 for trend), said Eunyoung Cho, Sc.D., of Brigham and Women's Hospital and Harvard, and colleagues.
Because choline is involved in the one-carbon metabolism process like other nutrients, such as folate, that decrease risk of adenoma, it was expected to do the same, they wrote in the Aug. 7 Journal of the National Cancer Institute.
But the findings may just be the latest in a series of surprises with initially promising chemopreventive agents, including ß-carotene and vitamin E, commented Regina Ziegler, Ph.D., and Unhee Lim, Ph.D., of the National Cancer Institute in Bethesda, Md., in an accompanying editorial.
"Clearly, one-carbon metabolism and its role in carcinogenesis is more complicated than originally anticipated, and our understanding of the underlying mechanisms is probably incomplete," they wrote. "More research, and caution in developing public health policy and guidance, is warranted."
The researchers analyzed food intake questionnaire responses from 39,246 women in the Nurses' Health Study who reported having undergone colonoscopy or sigmoidoscopy during the study.
Intake of choline and its metabolite, betaine, was estimated from biennial food frequency questionnaires.
The mean energy-adjusted choline intake was 331 mg/day, which is lower than the less than 425 mg/d recommended for women by the Institute of Medicine. Major food sources of the nutrient were red meat (18%), eggs (13%), poultry (9%), and milk (9%).
The mean energy-adjusted betaine intake was 189 mg/day. Major food sources were spinach (34%), white bread (8%), breakfast cereal (8%), pasta (7%), and dark bread (7%).
Although all women were free of cancer and colorectal polyps initially, 2,408 had adenoma documented from 1984 through 2002.
The association between colorectal adenoma and betaine intake was inverse, as the researchers had hypothesized. But, the association disappeared when adjusting for folate intake and other factors in the multivariate analysis (relative risk 0.90 for highest versus lowest intake quintile, P=0.09 for trend).
Unexpectedly, though, increasing choline intake was associated with elevated colorectal adenoma risk in multivariable analysis (P<0.001 for trend). The relative risks compared with the lowest intake quintile were:
1.03 for the quintile averaging 293 mg/day (95% confidence interval 0.90 to 1.18).
1.01 for the quintile averaging 315 mg/day (95% CI 0.88 to 1.16).
1.23 for the quintile averaging 340 mg/day (95% CI 1.07 to 1.41).
1.45 for the highest intake quintile averaging 383 mg/day, which is still lower than the recommended daily intake (95% CI 1.27 to 1.67).
Interactions with folate and alcohol intake, which have both been linked to methyl-group metabolism, did not modify the association between adenoma risk and choline (P=0.17 for interaction).
Nor did egg and red meat intake appear to be solely responsible. The elevated colorectal adenoma risk remained significant with increasing choline intake despite further adjusting for these major choline sources, and regardless of the level of red meat intake (P=0.0006 for trend).
Adjusting for other nutrients involved in methyl-group metabolism (such as methionine and vitamins B6 and B12) had little effect on the associations.
Although the choline results were unexpected based on its role as a methyl-group donor, the researchers suggested that the biologic basis could lie in choline's role in tumor development.
"Once a tumor is initiated, growth into a detectable adenoma depends in part on choline availability because choline is needed to make membranes in all rapidly growing cells," they wrote.
Few epidemiologic studies have looked at dietary choline and betaine, and the observations could be caused by other components of diets high in choline and betaine. So, more epidemiologic studies are needed to confirm the findings in other populations and in men, Dr. Cho and colleagues said.
Also, since the study looked only at adenoma, "studies of choline and betaine in relation to colorectal cancer should be undertaken," they added.
The study was funded by grants from the National Institutes of Health and the Department of Agriculture. The researchers reported no conflicts of interest.Primary source: Journal of the National Cancer InstituteSource reference: Cho E, et al "Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women" J Natl Cancer Inst 2007;99:1224-1231. Additional source: Journal of the National Cancer InstituteSource reference: Ziegler RG, Lim U "One-Carbon Metabolism, Colorectal Carcinogenesis, Chemoprevention-with Caution" J Natl Cancer Inst 2007;99:1214-1215.