{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:37:54Z","timestamp":1791419874545,"version":"4.3.3"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T00:00:00Z","timestamp":1476662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>B vitamins play an essential role in DNA synthesis and methylation, and may protect against oesophageal and gastric cancers. In this case-cohort study, subjects were enrolled from the General Population Nutrition Intervention Trial in Linxian, China. Subjects included 498 oesophageal squamous cell carcinomas (OSCCs), 255 gastric cardia adenocarcinomas (GCAs), and an age- and sex-matched sub-cohort of 947 individuals. Baseline serum riboflavin, pyridoxal phosphate (PLP), folate, vitamin B12, and flavin mononucleotide (FMN) were measured for all subjects. We estimated the associations with Cox proportional hazard models, with adjustment for potential confounders. Compared to those in the lowest quartile of serum riboflavin, those in the highest had a 44% lower risk of OSCC (HR: 0.56, 95% CI: 0.41 to 0.75). Serum vitamin B12 as a continuous variable was observed to be significantly inversely associated with OSCC (HR: 0.95, 95% CI: 0.89 to 1.01, <jats:italic>P<\/jats:italic> for score test\u2009=\u20090.041). Higher serum FMN levels were significantly associated with increased risk of OSCC (HR: 1.08, 95% CI: 1.01 to 1.16) and GCA (HR: 1.09, 95% CI: 1.00 to 1.20). Our study prompted that B vitamins have the potential role as chemopreventive agents for upper gastrointestinal cancers.<\/jats:p>","DOI":"10.1038\/srep35281","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T11:06:03Z","timestamp":1476702363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Prospective study of serum B vitamins levels and oesophageal and gastric cancers in China"],"prefix":"10.1038","volume":"6","author":[{"given":"Jiansong","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford M.","family":"Dawsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip R.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Selhub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlin","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian C.","family":"Abnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,10,17]]},"reference":[{"key":"BFsrep35281_CR1","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1001\/jama.2010.808","volume":"303","author":"M Johansson","year":"2010","unstructured":"Johansson, M. et al. Serum B vitamin levels and risk of lung cancer. JAMA. 303, 2377\u20132385 (2010).","journal-title":"JAMA."},{"key":"BFsrep35281_CR2","doi-asserted-by":"publisher","first-page":"4632","DOI":"10.1200\/JCO.2004.07.151","volume":"22","author":"PM Das","year":"2004","unstructured":"Das, P. M. & Singal, R. DNA methylation and cancer. J Clin Oncol. 22, 4632\u20134642 (2004).","journal-title":"J Clin Oncol."},{"key":"BFsrep35281_CR3","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1080\/01635581.2011.539315","volume":"63","author":"AC Mamede","year":"2011","unstructured":"Mamede, A. C. et al. The role of vitamins in cancer: a review. Nutr Cancer. 63, 479\u2013494 (2011).","journal-title":"Nutr Cancer."},{"key":"BFsrep35281_CR4","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1158\/1055-9965.EPI-09-0141","volume":"18","author":"L Le Marchand","year":"2009","unstructured":"Le Marchand, L. et al. Plasma levels of B vitamins and colorectal cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev. 18, 2195\u20132201 (2009).","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"BFsrep35281_CR5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1002\/mnfr.201500384","volume":"60","author":"W Kim","year":"2016","unstructured":"Kim, W. et al. Dietary folate, one-carbon metabolism-related genes, and gastric cancer risk in Korea. Mol Nutr Food Res. 60, 337\u2013345 (2016).","journal-title":"Mol Nutr Food Res."},{"key":"BFsrep35281_CR6","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1038\/bjc.2014.17","volume":"110","author":"Q Xiao","year":"2014","unstructured":"Xiao, Q. et al. 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\u20131333 (2014).","journal-title":"Br J Cancer."},{"key":"BFsrep35281_CR7","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1158\/1055-9965.EPI-14-0038","volume":"23","author":"SS Kweon","year":"2014","unstructured":"Kweon, S. S. et al. One-carbon metabolism dietary factors and distal gastric cancer risk in chinese women. Cancer Epidemiol Biomarkers Prev. 23, 1374\u20131382 (2014).","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"BFsrep35281_CR8","first-page":"619","volume":"10","author":"Y He","year":"2009","unstructured":"He, Y. et al. Effect of riboflavin-fortified salt nutrition intervention on esophageal squamous cell carcinoma in a high incidence area, China. Asian Pac J Cancer Prev. 10, 619\u2013622 (2009).","journal-title":"Asian Pac J Cancer Prev."},{"key":"BFsrep35281_CR9","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1080\/01635589709514541","volume":"27","author":"ZF Zhang","year":"1997","unstructured":"Zhang, Z. F. et al. Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutr Cancer. 27, 298\u2013309 (1997).","journal-title":"Nutr Cancer."},{"key":"BFsrep35281_CR10","first-page":"1055","volume":"10","author":"ST Mayne","year":"2001","unstructured":"Mayne, S. T. et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev. 10, 1055\u20131062 (2001).","journal-title":"Cancer Epidemiol Biomarkers Prev."},{"key":"BFsrep35281_CR11","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay, J. et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127, 2893\u20132917 (2010).","journal-title":"Int J Cancer."},{"key":"BFsrep35281_CR12","first-page":"337","volume":"36","author":"DI Thurnham","year":"1982","unstructured":"Thurnham, D. I., Rathakette, P., Hambidge, K. M., Munoz, N. & Crespi, M. Riboflavin, vitamin A and zinc status in Chinese subjects in a high-risk area for oesophageal cancer in China. Hum Nutr Clin Nutr. 36, 337\u2013349 (1982).","journal-title":"Hum Nutr Clin Nutr."},{"key":"BFsrep35281_CR13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1080\/01635588509513848","volume":"7","author":"DI Thurnham","year":"1985","unstructured":"Thurnham, D. I. et al. Comparison of riboflavin, vitamin A, and zinc status of Chinese populations at high and low risk for esophageal cancer. Nutr Cancer. 7, 131\u2013143 (1985).","journal-title":"Nutr Cancer."},{"key":"BFsrep35281_CR14","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/1047-2797(93)90078-I","volume":"3","author":"B Li","year":"1993","unstructured":"Li, B. et al. Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance. Ann Epidemiol. 3, 577\u2013585 (1993).","journal-title":"Ann Epidemiol."},{"key":"BFsrep35281_CR15","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1093\/jnci\/85.18.1483","volume":"85","author":"WJ Blot","year":"1993","unstructured":"Blot, W. J. et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin\/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 85, 1483\u20131492 (1993).","journal-title":"J Natl Cancer Inst."},{"key":"BFsrep35281_CR16","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1093\/jnci\/djp037","volume":"101","author":"YL Qiao","year":"2009","unstructured":"Qiao, Y. L. et al. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst. 101, 507\u2013518 (2009).","journal-title":"J Natl Cancer Inst."},{"key":"BFsrep35281_CR17","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1023\/A:1012533130596","volume":"7","author":"SD Mark","year":"2001","unstructured":"Mark, S. D. & Katki, H. Influence function based variance estimation and missing data issues in case-cohort studies. Lifetime Data Anal. 7, 331\u2013344 (2001).","journal-title":"Lifetime Data Anal."},{"key":"BFsrep35281_CR18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s10654-014-9974-4","volume":"30","author":"RS Kim","year":"2015","unstructured":"Kim, R. S. A new comparison of nested case-control and case-cohort designs and methods. Eur J Epidemiol. 30, 197\u2013207 (2015).","journal-title":"Eur J Epidemiol."},{"key":"BFsrep35281_CR19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0378-4347(87)80438-3","volume":"422","author":"A Araki","year":"1987","unstructured":"Araki, A. & Sako, Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 422, 43\u201352 (1987).","journal-title":"J Chromatogr."},{"key":"BFsrep35281_CR20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0027-5107(01)00070-7","volume":"475","author":"BN Ames","year":"2001","unstructured":"Ames, B. N. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 475, 7\u201320 (2001).","journal-title":"Mutat Res."},{"key":"BFsrep35281_CR21","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0304-3835(97)04662-4","volume":"114","author":"G van Poppel","year":"1997","unstructured":"van Poppel, G. & van den Berg, H. Vitamins and cancer. Cancer Lett. 114, 195\u2013202 (1997).","journal-title":"Cancer Lett."},{"key":"BFsrep35281_CR22","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S1383-5742(99)00056-3","volume":"428","author":"M Fenech","year":"1999","unstructured":"Fenech, M. Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat Res. 428, 299\u2013304 (1999).","journal-title":"Mutat Res."},{"key":"BFsrep35281_CR23","first-page":"1477","volume":"73","author":"AG Ershow","year":"1984","unstructured":"Ershow, A. G. et al. Compliance and nutritional status during feasibility study for an intervention trial in China. J Natl Cancer Inst. 73, 1477\u20131481 (1984).","journal-title":"J Natl Cancer Inst."},{"key":"BFsrep35281_CR24","first-page":"2280","volume":"48","author":"J Wahrendorf","year":"1988","unstructured":"Wahrendorf, J. et al. Blood, retinol and zinc riboflavin status in relation to precancerous lesions of the esophagus: findings from a vitamin intervention trial in the People\u2019s Republic of China. Cancer Res. 48, 2280\u20132283 (1988).","journal-title":"Cancer Res."},{"key":"BFsrep35281_CR25","doi-asserted-by":"publisher","first-page":"274","DOI":"10.3945\/jn.110.131235","volume":"141","author":"TI Ibiebele","year":"2011","unstructured":"Ibiebele, T. I. et al. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population. J Nutr. 141, 274\u2013283 (2011).","journal-title":"J Nutr."},{"key":"BFsrep35281_CR26","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1093\/annonc\/mdq356","volume":"22","author":"D Aune","year":"2011","unstructured":"Aune, D. et al. Dietary folate intake and the risk of 11 types of cancer: a case\u2013control study in Uruguay. Ann Oncol. 22, 444\u2013451 (2011).","journal-title":"Ann Oncol."},{"key":"BFsrep35281_CR27","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/clinchem\/48.9.1571","volume":"48","author":"S Hustad","year":"2002","unstructured":"Hustad, S. et al. Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation. Clin Chem. 48, 1571\u20131577 (2002).","journal-title":"Clin Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep35281.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep35281","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep35281.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:32:58Z","timestamp":1672885978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep35281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,17]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,16]]}},"alternative-id":["BFsrep35281"],"URL":"https:\/\/doi.org\/10.1038\/srep35281","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,17]]},"assertion":[{"value":"13 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35281"}}