Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.

PubMed  Google Scholar 

van Dijk AM, Coppens BJP, van Beers MA, Bruins Slot AS, Verstraete CJR, de Bruijne J, et al. Nutritional status in patients with hepatocellular carcinoma: potential relevance for clinical outcome. Eur J Intern Med. 2022;104:80–8.

Article  PubMed  Google Scholar 

Smith RJ. Nutrition and metabolism in hepatocellular carcinoma. Hepatobiliary Surg Nutr. 2013;2(2):89–96.

PubMed  PubMed Central  Google Scholar 

Mandair DS, Rossi RE, Pericleous M, Whyand T, Caplin M. The impact of diet and nutrition in the prevention and progression of hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2014;8(4):369–82.

Article  CAS  PubMed  Google Scholar 

Kim JY, Song M, Kim MS, Natarajan P, Do R, Myung W, et al. An atlas of associations between 14 micronutrients and 22 cancer outcomes: mendelian randomization analyses. BMC Med. 2023;21(1):316.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Antwi SO, Petrick JL, Campbell PT, Norez DA, Stevens VL, Liao LM, et al. One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: a prospective cohort study. Int J Cancer. 2020;147(8):2075–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fenech MF. Dietary reference values of individual micronutrients and nutriomes for genome damage prevention: current status and a road map to the future. Am J Clin Nutr. 2010;91(5):1438S-1454S.

Article  CAS  PubMed  Google Scholar 

Lyon P, Strippoli V, Fang B, Cimmino L. B vitamins and one-carbon metabolism: implications in human health and disease. Nutrients. 2020;12(9):2867.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Areekul S, Hitanant S, Panatampon P, Chantachum Y. Serum vitamin B12 and folate levels, vitamin B12 and folic acid binding proteins in patients with primary carcinoma of the liver. Southeast Asian J Trop Med Public Health. 1977;8(4):519–24.

CAS  PubMed  Google Scholar 

Kuo CS, Lin CY, Wu MY, Lu CL, Huang RF. Relationship between folate status and tumour progression in patients with hepatocellular carcinoma. Br J Nutr. 2008;100(3):596–602.

Article  CAS  PubMed  Google Scholar 

Malaguarnera G, Catania VE, Bertino G, Drago F, Madeddu R, Bonfiglio C, et al. Serum folate deficiency in HCV related hepatocellular carcinoma. Sci Rep. 2022;12(1):5025.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fang AP, Liu ZY, Liao GC, Chen PY, Wang XY, Zhang DM, et al. Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study. Br J Nutr. 2019;121(12):1376–88.

Article  CAS  PubMed  Google Scholar 

Ulrich CM, Potter JD. Folate and cancer–timing is everything. JAMA. 2007;297(21):2408–9.

Article  CAS  PubMed  Google Scholar 

Sharma R, Ali T, Kaur J. Folic acid depletion as well as oversupplementation helps in the progression of hepatocarcinogenesis in HepG2 cells. Sci Rep. 2022;12(1):16617.

Article  PubMed  PubMed Central  Google Scholar 

Arendt JFB, Pedersen L, Nexo E, Sørensen HT. Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study. J Natl Cancer Inst. 2013;105(23):1799–805.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin CY, Kuo CS, Lu CL, Wu MY, Huang RFS. Elevated serum vitamin B(12) levels in association with tumor markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma. Nutr Cancer. 2010;62(2):190–7.

Article  CAS  PubMed  Google Scholar 

Cui LH, Quan ZY, Piao JM, Zhang TT, Jiang MH, Shin MH, et al. Plasma folate and vitamin B12 levels in patients with hepatocellular carcinoma. Int J Mol Sci. 2016;17(7):1032.

Article  PubMed  PubMed Central  Google Scholar 

Boachie J, Adaikalakoteswari A, Goljan I, Samavat J, Cagampang FR, Saravanan P. Intracellular and tissue levels of vitamin B12 in hepatocytes are modulated by CD320 receptor and TCN2 transporter. Int J Mol Sci. 2021;22(6):3089.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lemos C, Kathmann I, Giovannetti E, Beliën JAM, Scheffer GL, Calhau C, et al. Cellular folate status modulates the expression of BCRP and MRP multidrug transporters in cancer cell lines from different origins. Mol Cancer Ther. 2009;8(3):655–64.

Article  CAS  PubMed  Google Scholar 

Fenech M. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutat Res. 2012;733(1–2):21–33.

Article  CAS  PubMed  Google Scholar 

Terzis AJ, Fiskerstrand T, Refsum H, Ueland PM, Arnold H, Bjerkvig R. Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs. Int J Cancer. 1993;54(1):112–8.

Article  CAS  PubMed  Google Scholar 

Siu MKY, Kong DSH, Chan HY, Wong ESY, Ip PPC, Jiang L, et al. Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome. PLoS ONE. 2012;7(11):e47201.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goyal H, Sharma R, Lamba D, Kaur J. Folic acid depletion along with inhibition of the PERK arm of endoplasmic reticulum stress pathway promotes a less aggressive phenotype of hepatocellular carcinoma cells. Mol Cell Biochem. 2023;478(9):2057–68.

Article  CAS  PubMed  Google Scholar 

Schaeffer D, Somarelli JA, Hanna G, Palmer GM, Garcia-Blanco MA. Cellular migration and invasion uncoupled: increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition. Mol Cell Biol. 2014;34(18):3486–99.

Article  PubMed  PubMed Central  Google Scholar 

Strickland KC, Krupenko NI, Krupenko SA. Molecular mechanisms underlying the potentially adverse effects of folate. Clin Chem Lab Med. 2013;51(3):607–16.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim YI. Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer? Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2004;13(4):511–9.

CAS  Google Scholar 

Chern CL, Huang RF, Chen YH, Cheng JT, Liu TZ. Folate deficiency-induced oxidative stress and apoptosis are mediated via homocysteine-dependent overproduction of hydrogen peroxide and enhanced activation of NF-kappaB in human Hep G2 cells. Biomed Pharmacother Biomed Pharmacother. 2001;55(8):434–42.

Article  CAS  PubMed  Google Scholar