Investigator Names and Contact Information
Daniel Caños, PhD, MPH
Dietary choline and betaine deficiencies decrease S-adenosylmethionine (SAM) concentrations which results in DNA hypomethylation. DNA hypomethylation may result in increased expression of oncogenes and an increased risk of DNA mutations, thus providing a basis for primary tumor growth and metastasis. Associations between DNA hypomethylation and colorectal, breast, and lung cancers have been reported. Betaine and choline intake may also be associated with coronary heart disease (CHD) and ischemic stroke risk through an atherogenic homocysteine methylation pathway. No studies have examined the relationship between these outcomes and habitual dietary choline and betaine intake. Until recently there were insufficient analytical data to estimate choline intake in populations. We will estimate the association between dietary total choline and betaine intake and the risk of cancer (colorectal; lung; invasive breast) and atherothrombotic (CHD; ischemic stroke) endpoints in the Women’s Health Initiative (WHI) Observational Study and the WHI Dietary Modification trial data collected over 8-12 years of follow-up. Food consumption data, quantified from the WHI Food Frequency Questionnaire will be converted into estimates of daily intake of total choline and betaine using the United States Department of Agriculture conversion values. If confirmed, the hypothesized association with chronic disease endpoints would suggest targets for primary prevention.
1. Describe the distribution of choline and betaine intake in both the WHI Observational Study and the WHI Dietary Modification trial at baseline, based on the WHI Food Frequency Questionnaire.
2. Estimate the relationship of dietary total choline and betaine intake separately with outcomes including to each of coronary heart disease, incident ischemic stroke, colorectal cancer, lung cancer, and invasive breast cancer within the WHI Observational Study.
3. Estimate the error in the measurement of betaine, choline, folate, B6 and B12from the WHI Food Frequency Questionnaire by comparing four-day food records to the WHI FFQ administered at one year within a subsample of the Dietary Modification trial participants.
4. Correct the estimated association of choline and betaine with the chronic end points for measurement error in the exposure variable(s)