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.
References
[1]
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.
[2]
Boffetta P, Hashibe M, La Vecchia C, Zatonski W, Rehm J (2006) The burden of cancer attributable to alcohol drinking. Int J Cancer 119: 884–887.
[3]
Dong C, Yoon YH, Chen CM, Yi HY (2011) Heavy alcohol use and premature death from hepatocellular carcinoma in the United States, 1999-2006. J Stud Alcohol Drugs 72: 892–902.
[4]
Shimazu T, Sasazuki S, Wakai K, Tamakoshi A, Tsuji I, et al. (2012) Alcohol drinking and primary liver cancer: a pooled analysis of four Japanese cohort studies. Int J Cancer 130: 2645–2653.
[5]
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.
[6]
Choi SW, Mason JB (2000) Folate and carcinogenesis: an integrated scheme. J Nutr 130: 129–132.
[7]
Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10: 66–88.
[8]
Stover PJ (2004) Physiology of folate and vitamin B12 in health and disease. Nutr Rev 62: S3–12; discussion S13.
[9]
Friso S, Choi SW (2005) Gene-nutrient interactions in one-carbon metabolism. Curr Drug Metab 6: 37–46.
[10]
Heinen MM, Verhage BA, Ambergen TA, Goldbohm RA, van den Brandt PA (2009) Alcohol consumption and risk of pancreatic cancer in the Netherlands cohort study. Am J Epidemiol 169: 1233–1242.
[11]
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.
[12]
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.
[13]
Persson EC, Schwartz LM, Park Y, Trabert B, Hollenbeck AR, et al. (2013) Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev 22: 415–421.
[14]
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.
[15]
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.
[16]
Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124: 17–27.
[17]
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.
[18]
Araki A, Sako Y (1987) Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 422: 43–52.
[19]
Zempleni J, Link G, Kubler W (1992) The transport of thiamine, riboflavin and pyridoxal 5′-phosphate by human placenta. Int J Vitam Nutr Res 62: 165–172.
[20]
Fears TR, Ziegler RG, Donaldson JL, Falk RT, Hoover RN, et al. (2002) Reproducibility studies and interlaboratory concordance for androgen assays of male plasma hormone levels. Cancer Epidemiol Biomarkers Prev 11: 785–789.
[21]
Anderson OS, Sant KE, Dolinoy DC (2012) Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J Nutr Biochem 23: 853–859.
[22]
Halsted CH, Villanueva JA, Devlin AM, Chandler CJ (2002) Metabolic interactions of alcohol and folate. J Nutr 132: 2367S–2372S.
[23]
Seitz HK, Stickel F (2007) Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer 7: 599–612.
[24]
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.
[25]
Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH, et al. (2002) Folic acid intake from fortification in United States exceeds predictions. J Nutr 132: 2792–2798.
[26]
Piyathilake CJ, Macaluso M, Hine RJ, Richards EW, Krumdieck CL (1994) Local and systemic effects of cigarette smoking on folate and vitamin B-12. Am J Clin Nutr 60: 559–566.
[27]
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.
[28]
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.
