Background Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk. Results Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer. Conclusions The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.
Schutze M, Boeing H, Pischon T, Rehm J, Kehoe T, et al. (2011) Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study. BMJ 342: d1584.
Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, et al. (2011) Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study. J Natl Cancer Inst 103: 1686–1695.
Stolzenberg-Solomon RZ, Chang SC, Leitzmann MF, Johnson KA, Johnson C, et al. (2006) Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr 83: 895–904.
Ibiebele TI, Hughes MC, Pandeya N, Zhao Z, Montgomery G, et al. (2011) High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr 141: 274–283.
The ATBC Cancer Prevention Study Group (1994) The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. The ATBC Cancer Prevention Study Group. Ann Epidemiol 4: 1–10.
Pietinen P, Hartman AM, Haapa E, Rasanen L, Haapakoski J, et al. (1988) Reproducibility and validity of dietary assessment instruments. I. A self-administered food use questionnaire with a portion size picture booklet. Am J Epidemiol 128: 655–666.
Shin-Buehring YS, Stuempfig L, Pouget E, Rahm P, Schaub J (1981) Characterization of galactose-1-phosphate uridyl-transferase and galactokinase in human organs from the fetus and adult. Clin Chim Acta 112: 257–265.
Welzel TM, Katki HA, Sakoda LC, Evans AA, London WT, et al. (2007) Blood folate levels and risk of liver damage and hepatocellular carcinoma in a prospective high-risk cohort. Cancer Epidemiol Biomarkers Prev 16: 1279–1282.
Gabriel HE, Crott JW, Ghandour H, Dallal GE, Choi SW, et al. (2006) Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. Am J Clin Nutr 83: 835–841.
Mannino DM, Mulinare J, Ford ES, Schwartz J (2003) Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey. Nicotine Tob Res 5: 357–362.