Journal of the National Cancer Institute Advance Access published online on August 8, 2007
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm082
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© The Author 2007. Published by Oxford University Press.
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Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women
Affiliations of authors: Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (EC, WCW, CSF, ATC, ELG); Departments of Nutrition (WCW, KW, ELG) and Epidemiology (WCW, ELG), Harvard School of Public Health, Boston, MA; Department of Surgery and Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, MO (GAC); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (CSF); Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA (ATC); Department of Nutrition, University of North Carolina, Chapel Hill, NC (SHZ)
Correspondence to: Eunyoung Cho, ScD, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115 (e-mail: eunyoung.cho{at}channing.harvard.edu).
Background: Choline and betaine are involved in methyl-group metabolism as methyl-group donors; thus, like folate, another methyl-group donor, they may be associated with a reduced risk of colorectal adenomas. No epidemiologic study has examined the association of intake of these nutrients and colorectal adenoma risk.
Methods: We investigated the relationship between intakes of choline and betaine and risk of colorectal adenoma in US women enrolled in the Nurses’ Health Study. Dietary intake was measured by food-frequency questionnaires, and individual intakes of choline and betaine were calculated by multiplying the frequency of consumption of each food item by its choline and betaine content and summing the nutrient contributions of all foods. Logistic regression models were used to calculate adjusted odds ratios (as approximations for relative risks) and 95% confidence intervals (CIs) of colorectal adenoma. All statistical tests were two-sided.
Results: Among 39246 women who were initially free of cancer or polyps and who had at least one endoscopy from 1984 through 2002, 2408 adenoma cases were documented. Increasing choline intake was associated with an elevated risk of colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake, relative to the lowest quintile, were 1.03 (0.90 to 1.18), 1.01 (0.88 to 1.16), 1.23 (1.07 to 1.41), and 1.45 (1.27 to 1.67; Ptrend<.001). Betaine intake had a nonlinear inverse association with colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake were 0.94 (0.83 to 1.07), 0.85 (0.75 to 0.97), 0.86 (0.75 to 0.98), and 0.90 (95% CI = 0.78 to 1.04; Ptrend = .09). Among individual sources of choline, choline from phosphatidylcholine and from sphingomyelin were each positively related to adenoma risk.
Conclusions: Our findings do not support an inverse association between choline intake and risk of colorectal adenoma. The positive association between choline intake and colorectal adenoma that we observed could represent effects of other components in the foods from which choline was derived and should be investigated further.
| CONTEXT AND CAVEATS Prior knowledge Epidemiologic studies have suggested that lower dietary intake of folate and methionine and higher intake of alcohol are associated with an increased risk of colorectal adenoma (polyps in the colon or rectum that may develop into colorectal cancer). All of these dietary factors are involved in a biochemical pathway(s) referred to as one-carbon metabolism. Choline and betaine in the diet also affect one-carbon metabolism, but their association with the risk of colorectal cancer was not known. Study design Dietary intake of choline and betaine and incidence of colorectal adenoma were assessed by a questionnaire that was sent to a large group of female nurses every 2 years, and statistical methods were used to assess the association between choline intake and the risk of colorectal adenoma. Contribution Increased dietary intake of choline was associated with an elevated risk of colorectal adenoma. The association with betaine intake was not clear. Implications Additional work will be needed to clarify the relationship between choline and risk of colorectal adenoma. Limitations Other components of the diet, the intakes of which are highly correlated with choline consumption, may be the source of the increased risk of colorectal adenoma that was observed.
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Manuscript received December 6, 2006; revised June 5, 2007; accepted June 26, 2007.
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J Natl Cancer Inst 2007 99: 1214-1215.
J Natl Cancer Inst 2007 99: 1213.
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