Folate intake, MTHFR C677T polymorphism, alcohol consumption, and risk for sporadic colorectal adenoma (United States) Sonia M. Boyapati 1 , Roberd M. Bostick 2,3, *, Katherine A. McGlynn 4 , Michael F. Fina 5 , Walter M. Roufail 6 , Kim R. Geisinger 6 , James R. Hebert 3 , Ann Coker 7 & Michael Wargovich 8 1 Division of General Internal Medicine, Department of Medicine, Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, TN, USA; 2 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA; 3 Department of Hematology and Oncology, School of Medicine, Emory University, Atlanta, GA, USA; 4 National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA; 5 Forsyth Medical Specialists, PA, Winston-Salem, NC, USA; 6 Wake Forest University, Winston-Salem, NC, USA; 7 School of Public Health, University of Texas, Houston, TX, USA; 8 Department of Pathology, School of Medicine, University of South Carolina, USA Received 29 April 2003; accepted in revised form 4 March 2004 Key words: alcohol, colorectal adenoma, folate, MTHFR polymorphism. Abstract Objective: The purpose of this study was to investigate whether folate intake is associated with risk for incident sporadic colorectal adenoma, and whether the association differs according to methylenetetrahydrofolate reductase (MTHFR) genotypes or is modified by intakes of alcohol or other micronutrients in the folate metabolism pathway. Methods: The authors analyzed data from a colonoscopy-based case–control study (n ¼ 177 cases, 228 controls) conducted in North Carolina between 1995 and 1997. Results: The multivariate-adjusted odds ratio (OR) comparing the highest to lowest tertile of total folate intake was 0.61 (95% confidence interval [CI] 0.35–1.05); for MTHFR C677T polymorphism CT and TT genotypes relative to the CC genotype they were, respectively, 1.09 (CI: 0.71–1.66) and 0.68 (CI: 0.29–1.61); and for heavy drinkers (>3 drinks/week) compared to non-drinkers it was 1.67 (CI: 1.00–2.81). The multivariate-adjusted ORs comparing the highest to lowest tertile of total folate intake according to those with the MTHFR CC, CT, and TT genotypes, were, respectively, 0.65 (CI: 0.30–1.39), 0.57 (CI: 0.23–1.44), and 0.22 (CI: 0.02–3.19). For those in the lowest tertile of folate intake who drank more than three drinks a week compared to those who were in the highest tertile of folate intake and did not drink alcohol the OR was 6.54 (CI: 1.96–21.80). There was no substantial evidence for interactions of folate with intakes of methionine, vitamins B2, B6, or B12. Conclusions: These data are consistent with hypotheses and previous findings that higher folate intake may reduce risk for colorectal neoplasms, perhaps especially among those who consume more alcohol. Introduction Many, but not all, epidemiological studies have found diets high in fruits and vegetables to be associated with a decreased risk for colon cancer [1]. Specific micronutri- ents found in fruits and vegetables are thought to contribute to the observed inverse associations. In particular, fruits and vegetables are a major source of folate. Folate is a key component in nucleic acid synthesis, methionine regeneration, and phases of amino acid metabolism [2]. Folate deficiency can cause DNA damage in the form of uracil misincorporation and impaired DNA repair [3–5]. The majority of prospective epidemiological studies have found that high folate intake is associated with reduced risk both for colon cancer [6–8] and colorectal adenoma [9]. Several polymorphisms in critical enzymes involved in folate metabolism have recently been identified. * Address correspondence to: Roberd M. Bostick, MD, MPH, Department of Epidemiology, Department of Hematology and Oncology Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, USA Atlanta, GA 30322, Ph.: +1-404-727-2671; Fax.: +1-404-727-8737; E-mail: rmbosti@sph.emory.edu Cancer Causes and Control 15: 493–501, 2004. 493 Ó 2004 Kluwer Academic Publishers. Printed in the Netherlands.