{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:26:11Z","timestamp":1788895571489,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T00:00:00Z","timestamp":1455580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81001197"],"award-info":[{"award-number":["81001197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Specialty Construction of Clinical Project","award":["#2013-544"],"award-info":[{"award-number":["#2013-544"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Esophageal cancer (EC) and gastric cancer (GC) are common cancers and leading causes of cancer deaths worldwide. Many studies have investigated the association between dietary flavonols intake and the risk of EC and GC, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to assess the association and derive a more precise estimation. Methods: The Cochrane, PubMed and Embase databases were searched to identify articles published through January 2016 that met the predetermined inclusion criterion. Twelve studies involving 4593 patients and 519,378 controls were included. Results: The summary odds ratios (ORs) of EC, GC and the two combined were respectively 0.88 (95% CI: 0.73\u20131.08), 0.80 (95% CI: 0.70\u20130.91) and 0.83 (95% CI: 0.74\u20130.92) for the highest category of dietary flavonols intake compared with the lowest. No significant heterogeneities were observed in these studies. Further analysis showed that the pooled ORs of EC and GC for cohort, population-based case-control and hospital-based case-control studies were 0.90 (95% CI: 0.61\u20131.34), 0.92 (95% CI: 0.72\u20131.18), 0.68 (95% CI: 0.38\u20131.24) and 0.83 (95% CI: 0.65\u20131.06), 0.84 (95% CI: 0.45\u20131.59), 0.70 (95% CI: 0.56\u20130.88). The subgroup analyses revealed a significant association of flavonol intake with a reduced risk of noncardia gastric adenocarcinoma but not gastric cardia adenocarcinoma. Moreover, significant inverse associations of flavonol intake with GC risk were observed in women but not in men, in smokers but not in nonsmokers, in European populations but not in American populations. Similarly, a significant inverse association of flavonols intake with EC risk was also observed in smokers but not in nonsmokers. Conclusion: High intake of dietary flavonols is significantly related to a reduced risk of GC, especially in women and smokers.<\/jats:p>","DOI":"10.3390\/nu8020091","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T10:39:15Z","timestamp":1455619155000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Dietary Flavonols Intake and Risk of Esophageal and Gastric Cancer: A Meta-Analysis of Epidemiological Studies"],"prefix":"10.3390","volume":"8","author":[{"given":"Yan","family":"Xie","sequence":"first","affiliation":[{"name":"Stem Cell Biology and Therapy Laboratory, Lab medicine of Maternity and Child Care Hospital of Yubei District, Ministry of Education Key Laboratory of Child Development and Disorders, the Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Orthopedic Department II, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, the Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Su","sequence":"additional","affiliation":[{"name":"Orthopedic Department II, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, the Children\u2019s Hospital of Chongqing Medical University, Chongqing 400014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"ref_1","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Dicker, D., Pain, A., Hamavid, H., Moradi-Lakeh, M., MacIntyre, M.F., Allen, C., Hansen, G., and Woodbrook, R. (2015). The Global Burden of Cancer 2013. JAMA Oncol., 1, 505\u2013527."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/(SICI)1097-0142(19981115)83:10<2049::AID-CNCR1>3.0.CO;2-2","article-title":"Changing patterns in the incidence of esophageal and gastric carcinoma in the United States","volume":"83","author":"Devesa","year":"1998","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3322\/caac.20141","article-title":"Cancers with increasing incidence trends in the United States: 1999 through 2008","volume":"62","author":"Simard","year":"2012","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1046\/j.1365-2168.1999.01082.x","article-title":"Adenocarcinomas of the distal oesophagus and gastric cardia are one clinical entity. Rotterdam Oesophageal Tumour Study Group","volume":"86","author":"Wijnhoven","year":"1999","journal-title":"Br. J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1053\/j.gastro.2015.02.007","article-title":"Diet and upper gastrointestinal malignancies","volume":"148","author":"Abnet","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"283","DOI":"10.7314\/APJCP.2015.16.1.283","article-title":"Is there any relationship between food habits in the last two decades and gastric cancer in North-Western Iran?","volume":"16","author":"Somi","year":"2015","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.7314\/APJCP.2014.15.13.5293","article-title":"Salt processed food and gastric cancer in a Chinese population","volume":"15","author":"Lin","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.nut.2013.10.009","article-title":"Flavonol intake and stroke risk: A meta-analysis of cohort studies","volume":"30","author":"Wang","year":"2014","journal-title":"Nutrition"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chang, H., Xie, Q., Zhang, Q.Y., Peng, X.L., Zhu, J.D., and Mi, M.T. (2013). Flavonoids, flavonoid subclasses and breast cancer risk: A meta-analysis of epidemiologic studies. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054318"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/nure.12152","article-title":"Molecular and physiological actions of quercetin: need for clinical trials to assess its benefits in human disease","volume":"72","author":"Miles","year":"2014","journal-title":"Nutr. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ejmech.2015.04.063","article-title":"Novel myricetin derivatives: Design, synthesis and anticancer activity","volume":"97","author":"Xue","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/oxfordjournals.epirev.a036298","article-title":"Quantitative methods in the review of epidemiologic literature","volume":"9","author":"Greenland","year":"1987","journal-title":"Epidemiol. Rev."},{"key":"ref_14","first-page":"719","article-title":"Statistical aspects of the analysis of data from retrospective studies of disease","volume":"22","author":"Mantel","year":"1959","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control. Clin. Trials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/ng749","article-title":"Replication validity of genetic association studies","volume":"29","author":"Ioannidis","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/bjc.2015.25","article-title":"Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA)","volume":"112","author":"Petrick","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/aje\/kwt026","article-title":"Dietary flavonoid intake and esophageal cancer risk in the European prospective investigation into cancer and nutrition cohort","volume":"178","author":"Vermeulen","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/ijc.24421","article-title":"Flavonoid consumption and esophageal cancer among black and white men in the United States","volume":"125","author":"Bobe","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/ijc.22499","article-title":"Flavonoids and risk of squamous cell esophageal cancer","volume":"120","author":"Rossi","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1093\/annonc\/mdq390","article-title":"Dietary quercetin intake and risk of gastric cancer: Results from a population-based study in Sweden","volume":"22","author":"Serafini","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.3390\/nu6114961","article-title":"Dietary flavonoids and gastric cancer risk in a Korean population","volume":"6","author":"Woo","year":"2014","journal-title":"Nutrients"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.3945\/ajcn.112.037358","article-title":"Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study","volume":"96","author":"Agudo","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1007\/s10552-010-9588-4","article-title":"Flavonoids, proanthocyanidins, and the risk of stomach cancer","volume":"21","author":"Rossi","year":"2010","journal-title":"Cancer Causes Control."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1023\/B:CACO.0000016619.18041.b0","article-title":"Flavonoids, vitamin C and adenocarcinoma of the stomach","volume":"15","author":"Lagiou","year":"2004","journal-title":"Cancer Causes Control."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/ajcn\/76.3.560","article-title":"Flavonoid intake and risk of chronic diseases","volume":"76","author":"Knekt","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1023\/A:1012232008016","article-title":"Flavonol and flavone intake and the risk of cancer in male smokers (Finland)","volume":"12","author":"Hirvonen","year":"2001","journal-title":"Cancer Causes Control."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1023\/A:1008867108960","article-title":"Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain","volume":"10","author":"Gonzalez","year":"1999","journal-title":"Cancer Causes Control."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3322\/caac.21254","article-title":"Cancer statistics, 2015","volume":"65","author":"Siegel","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1158\/1055-9965.EPI-15-0134","article-title":"Prevalence of major risk factors and use of screening tests for cancer in the United States","volume":"24","author":"Fedewa","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S181","DOI":"10.4103\/0975-7406.155895","article-title":"Naturally occurring products in cancer therapy","volume":"7","author":"Rajesh","year":"2015","journal-title":"J. Pharm. Bioallied. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1039\/C4FO00413B","article-title":"The pleiotropic flavonoid quercetin: from its metabolism to the inhibition of protein kinases in chronic lymphocytic leukemia","volume":"5","author":"Russo","year":"2014","journal-title":"Food Funct."},{"key":"ref_33","first-page":"1736","article-title":"Protective effects of curcumin and quercetin during benzo(a)pyrene induced lung carcinogenesis in mice","volume":"19","author":"Liu","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"494","DOI":"10.2174\/1389557514666140622204037","article-title":"Dependence of DPPH radical scavenging activity of dietary flavonoid quercetin on reaction environment","volume":"14","author":"Sak","year":"2014","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1167\/iovs.10-5777","article-title":"Quercetin induces the expression of peroxiredoxins 3 and 5 via the Nrf2\/NRF1 transcription pathway","volume":"52","author":"Miyamoto","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"826","DOI":"10.2174\/1871520614666140521122932","article-title":"Nanoparticle-delivered quercetin for cancer therapy","volume":"14","author":"Men","year":"2014","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.taap.2012.07.022","article-title":"Quercetin 3-O-methyl ether protects FL83B cells from copper induced oxidative stress through the PI3K\/Akt and MAPK\/Erk pathway","volume":"264","author":"Tseng","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.phrs.2015.06.006","article-title":"Quercetin inhibits the mTORC1\/p70S6K signaling-mediated renal tubular epithelial-mesenchymal transition and renal fibrosis in diabetic nephropathy","volume":"99","author":"Lu","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s10549-012-2323-y","article-title":"Dual association between polyphenol intake and breast cancer risk according to alcohol consumption level: a prospective cohort study","volume":"137","author":"Touvier","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Milenkovic, D., Vanden Berghe, W., Boby, C., Leroux, C., Declerck, K., Szarc vel Szic, K., Heyninck, K., Laukens, K., Bizet, M., and Defrance, M. (2014). Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095527"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, G., Wulan, H., Song, Z., Paik, P.A., Tsao, M.L., Goodman, G.M., MacEachern, P.T., Downey, R.S., Jankowska, A.J., and Rabinowitz, Y.M. (2015). Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134591"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S1368-8375(98)00061-X","article-title":"Diet and risk of cancer of the upper aerodigestive tract--II","volume":"35","author":"Ronco","year":"1999","journal-title":"Nutrients.Oral Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3748\/wjg.v19.i7.1011","article-title":"Dietary flavonoid intake and risk of stomach and colorectal cancer","volume":"19","author":"Woo","year":"2013","journal-title":"World J. Gastroenterol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/8\/2\/91\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:19:12Z","timestamp":1760210352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/8\/2\/91"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,16]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,2]]}},"alternative-id":["nu8020091"],"URL":"https:\/\/doi.org\/10.3390\/nu8020091","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,16]]}}}