No CrossRef data available.
Article contents
Interaction between dietary nutrients related to one-carbon metabolism intakes and AHCY rs819173 polymorphism in the risk of gastric cancer: a case–control study in Korea
Published online by Cambridge University Press: 27 August 2025
Abstract
B vitamin and methionine intake may influence cancer development, but their link to gastric cancer (GC) risk is unclear. Nutrients related to one-carbon metabolism (OCM) have been shown to be associated with S-adenosylhomocysteine hydrolase (AHCY), one of the most crucial enzymes in OCM, which is regulated by the AHCY gene. Thus, we hypothesised that a higher intake of total nutrients related to OCM may reduce the risk of GC, and this preventative effect may interact with the AHCY rs819173 polymorphism. We conducted a case–control study at the National Cancer Center in Korea, involving 371 cases and 738 controls, aiming to determine the interaction between the AHCY rs819173 polymorphism and nutrients related to OCM intakes in GC risk. Dietary vitamin B and methionine intakes were collected using semi-quantitative FFQ (SQFFQ). The OR and 95 % CI were calculated using unconditional logistic regression models. Higher intake of total nutrients related to OCM was found to be inversely associated with GC risk (adjusted OR (aOR) = 0·57, 95 % CI 0·37, 0·86, Pfor trend = 0·009). No significant association between the AHCY rs819173 polymorphism and GC risk was found. In the dominant model of AHCY rs819173, participants with major homozygous (TT) and higher intake of nutrients related to OCM had a lower GC risk than those with lower intake (aOR = 0·49, 95 % CI 0·30, 0·81, P interaction = 0·015). Higher intakes of total vitamin B and methionine were proposed as potential protective nutrients against GC. Moreover, this association might be influenced by the presence of the AHCY rs819173 polymorphism.
Information
- Type
- Research Article
- Information
- Copyright
- © The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society
References
Sung, H, Ferlay, J, Siegel, RL, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71, 209–249.Google ScholarPubMed
Kang, MJ, Jung, KW, Bang, SH, et al. (2023) Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2020. Cancer Res Treat 55, 385–399.10.4143/crt.2023.447CrossRefGoogle ScholarPubMed
Tio, M, Andrici, J, Cox, MR, et al. (2014) Folate intake and the risk of upper gastrointestinal cancers: a systematic review and meta-analysis. J Gastroenterol Hepatol 29, 250–258.10.1111/jgh.12446CrossRefGoogle ScholarPubMed
Doll, R & Peto, R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 66, 1191–1308.CrossRefGoogle ScholarPubMed
Willett, WC (1995) Diet, nutrition, and avoidable cancer. Environ Health Perspect 103, 165–170.Google ScholarPubMed
Dugue, PA, Bassett, JK, Brinkman, MT, et al. (2019) Dietary intake of nutrients involved in one-carbon metabolism and risk of gastric cancer: a prospective study. Nutr Cancer 71, 605–614.10.1080/01635581.2019.1577982CrossRefGoogle ScholarPubMed
Lu, YT, Gunathilake, M, Lee, J, et al. (2022) Riboflavin intake, MTRR genetic polymorphism (rs1532268) and gastric cancer risk in a Korean population: a case-control study. Br J Nutr 127, 1026–1033.10.1017/S0007114521001811CrossRefGoogle Scholar
Kim, W, Woo, HD, Lee, J, et al. (2016) Dietary folate, one-carbon metabolism-related genes, and gastric cancer risk in Korea. Mol Nutr Food Res 60, 337–345.10.1002/mnfr.201500384CrossRefGoogle ScholarPubMed
Galvan-Portillo, MV, Cantoral, A, Onate-Ocana, LF, et al. (2009) Gastric cancer in relation to the intake of nutrients involved in one-carbon metabolism among MTHFR 677 TT carriers. Eur J Nutr 48, 269–276.10.1007/s00394-009-0010-5CrossRefGoogle Scholar
Khairan, P, Sobue, T, Eshak, ES, et al. (2022) Association of B vitamins and methionine intake with the risk of gastric cancer: the Japan public health center-based prospective study. Cancer Prev Res (Phila) 15, 101–110.10.1158/1940-6207.CAPR-21-0224CrossRefGoogle ScholarPubMed
Bassett, JK, Hodge, AM, English, DR, et al. (2012) Dietary intake of B vitamins and methionine and risk of lung cancer. Eur J Clin Nutr 66, 182–187.10.1038/ejcn.2011.157CrossRefGoogle ScholarPubMed
Xu, J & Sinclair, KD (2015) One-carbon metabolism and epigenetic regulation of embryo development. Reprod Fertil Dev 27, 667–676.10.1071/RD14377CrossRefGoogle ScholarPubMed
Newman, AC & Maddocks, ODK (2017) One-carbon metabolism in cancer. Br J Cancer 116, 1499–1504.10.1038/bjc.2017.118CrossRefGoogle ScholarPubMed
Clare, CE, Brassington, AH, Kwong, WY, et al. (2019) One-carbon metabolism: linking nutritional biochemistry to epigenetic programming of long-term development. Annu Rev Anim Biosci 7, 263–287.10.1146/annurev-animal-020518-115206CrossRefGoogle ScholarPubMed
Feng, Q, Keshtgarpour, M, Pelleymounter, LL, et al. (2009) Human S-adenosylhomocysteine hydrolase: common gene sequence variation and functional genomic characterization. J Neurochem 110, 1806–1817.10.1111/j.1471-4159.2009.06276.xCrossRefGoogle ScholarPubMed
Mahmoud, AM & Ali, MM (2019) Methyl donor micronutrients that modify DNA methylation and cancer outcome. Nutrients 11, 608.10.3390/nu11030608CrossRefGoogle ScholarPubMed
Chen, J, Yuan, L, Duan, YQ, et al. (2014) Impact of methylenetetrahydrofolate reductase polymorphisms and folate intake on the risk of gastric cancer and their association with Helicobacter pylori infection and tumor site. Genet Mol Res 13, 9718–9726.10.4238/2014.January.24.2CrossRefGoogle ScholarPubMed
Chang, SC, Chang, PY, Butler, B, et al. (2014) Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population. PLoS One 9, e109235.10.1371/journal.pone.0109235CrossRefGoogle ScholarPubMed
Zhao, T, Gu, D, Xu, Z, et al. (2015) Polymorphism in one-carbon metabolism pathway affects survival of gastric cancer patients: large and comprehensive study. Oncotarget 6, 9564–9576.CrossRefGoogle ScholarPubMed
Pyun, H, Gunathilake, M, Lee, J, et al. (2024) Functional annotation and gene set analysis of gastric cancer risk loci in a Korean population. Cancer Res Treat 56, 191–198.10.4143/crt.2022.958CrossRefGoogle Scholar
Levine, AJ, Figueiredo, JC, Lee, W, et al. (2010) A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 19, 1812–1821.10.1158/1055-9965.EPI-10-0151CrossRefGoogle ScholarPubMed
Tabassum, R, Jaiswal, A, Chauhan, G, et al. (2012) Genetic variant of AMD1 is associated with obesity in urban Indian children. PLoS One 7, e33162.10.1371/journal.pone.0033162CrossRefGoogle ScholarPubMed
Bae, JM (2020) Body mass index and risk of gastric cancer in Asian adults: a meta-epidemiological meta-analysis of population-based cohort studies. Cancer Res Treat 52, 369–373.10.4143/crt.2019.241CrossRefGoogle ScholarPubMed
Gunathilake, MN, Lee, J, Jang, A, et al. (2018) Physical activity and gastric cancer risk in patients with and without Helicobacter pylori infection in a Korean population: a hospital-based case-control study. Cancers (Basel) 10, 369.10.3390/cancers10100369CrossRefGoogle Scholar
Ahn, Y, Kwon, E, Shim, JE, et al. (2007) Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 61, 1435–1441.10.1038/sj.ejcn.1602657CrossRefGoogle ScholarPubMed
Lu, Y, Kweon, SA-O, Cai, Q, et al. (2019) Identification of novel loci and new risk variant in known loci for colorectal cancer risk in East Asians. Cancer Epidemiol Biomarkers Prev 29, 477–486.10.1158/1055-9965.EPI-19-0755CrossRefGoogle ScholarPubMed
Poursalehi, D, Lotfi, K, Mirzaei, S, et al. (2022) Association between methyl donor nutrients and metabolic health status in overweight and obese adolescents. Sci Rep 12, 17045.10.1038/s41598-022-21602-9CrossRefGoogle ScholarPubMed
Kadam, I, Dalloul, M, Hausser, J, et al. (2023) Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus. Clin Epigenet 15, 137.10.1186/s13148-023-01554-1CrossRefGoogle ScholarPubMed
Larsson, SC, Giovannucci, E & Wolk, A (2006) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131, 1271–1283.10.1053/j.gastro.2006.08.010CrossRefGoogle ScholarPubMed
Xiao, Q, Freedman, ND, Ren, J, et al. (2014) Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study. Br J Cancer 110, 1328–1333.10.1038/bjc.2014.17CrossRefGoogle Scholar
Kweon, SS, Shu, XO, Xiang, Y, et al. (2014) One-carbon metabolism dietary factors and distal gastric cancer risk in Chinese women. Cancer Epidemiol Biomarkers Prev 23, 1374–1382.10.1158/1055-9965.EPI-14-0038CrossRefGoogle ScholarPubMed
Lyon, P, Strippoli, V, Fang, B, et al. (2020) B vitamins and one-carbon metabolism: implications in human health and disease. Nutrients 12, 2867.10.3390/nu12092867CrossRefGoogle ScholarPubMed
Franco, CN, Seabrook, LJ, Nguyen, ST, et al. (2022) Simplifying the B complex: how vitamins B6 and B9 modulate one carbon metabolism in cancer and beyond. Metabolites 12, 961.10.3390/metabo12100961CrossRefGoogle Scholar
Pan, S, Fan, M, Liu, Z, et al. (2021) Serine, glycine and one-carbon metabolism in cancer (review). Int J Oncol 58, 158–170.10.3892/ijo.2020.5158CrossRefGoogle ScholarPubMed
Sanderson, SM, Gao, X, Dai, Z, et al. (2019) Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat Rev Cancer 19, 625–637.10.1038/s41568-019-0187-8CrossRefGoogle Scholar
Vizan, P, Di Croce, L & Aranda, S (2021) Functional and pathological roles of AHCY. Front Cell Dev Biol 9, 654344.10.3389/fcell.2021.654344CrossRefGoogle ScholarPubMed
Caudill, MA, Wang, JC, Melnyk, S, et al. (2001) Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice. J Nutr 131, 2811–2818.CrossRefGoogle ScholarPubMed
Baric, I, Fumic, K, Glenn, B, et al. (2004) S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci 101, 4234–4239.10.1073/pnas.0400658101CrossRefGoogle Scholar
Vugrek, O, Beluzic, R, Nakic, N, et al. (2009) S-adenosylhomocysteine hydrolase (AHCY) deficiency: two novel mutations with lethal outcome. Hum Mutat 30, E555–565.10.1002/humu.20985CrossRefGoogle ScholarPubMed
Honzík, T, Magner, M, Krijt, J, et al. (2012) Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles phosphomannomutase 2 deficiency. Mol Genet Metab 107, 611–613.10.1016/j.ymgme.2012.08.014CrossRefGoogle ScholarPubMed
Boczki, P, Colombo, M, Weiner, J, et al. (2024) Inhibition of AHCY impedes proliferation and differentiation of mouse and human adipocyte progenitor cells. Adipocyte 13, 2290218.CrossRefGoogle ScholarPubMed
Nguyen et al. supplementary material
Nguyen et al. supplementary material
File
51.3 KB