{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:43:34Z","timestamp":1790959414278,"version":"4.1.0"},"reference-count":42,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"unspecified","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":"crossref","award":["81573219"],"award-info":[{"award-number":["81573219"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"\n Purpose<\/jats:title>\n \n Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal\n EPHA5<\/jats:italic>\n methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the\n EPHA5<\/jats:italic>\n methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A total of 366 GC cases and 374 controls were selected as the subjects of this study to collect their environmental factors, and the\n EPHA5<\/jats:italic>\n methylation status was detected through the methylation-sensitive high-resolution melting method. Logistic regression analysis was utilized to evaluate the associations among\n EPHA5<\/jats:italic>\n methylation, environmental factors and GC risk. Meanwhile, the propensity score (PS) was used to adjust the imbalance of some independent variables.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n After PS adjustment,\n EPHA5<\/jats:italic>\n Pm (positive methylation) was more likely to increase the GC risk than\n EPHA5<\/jats:italic>\n Nm (negative methylation) (OR\n b<\/jats:sup>\n = 1.827, 95% CI [1.202\u20132.777],\n P<\/jats:italic>\n = 0.005).\n EPHA5<\/jats:italic>\n Pm had a more significant association with GC risk in the elderly (OR\n a<\/jats:sup>\n = 2.785, 95% CI [1.563\u20134.961],\n P<\/jats:italic>\n = 0.001) and\n H. pylori<\/jats:italic>\n -negative groups (OR\n a<\/jats:sup>\n = 2.758, 95% CI [1.369\u20135.555],\n P<\/jats:italic>\n = 0.005). Moreover, the combined effects of\n EPHA5<\/jats:italic>\n Pm and\n H. pylori<\/jats:italic>\n infection (OR\n c<\/jats:sub>\n a<\/jats:sup>\n = 3.543, 95% CI [2.233\u20135.621],\n P<\/jats:italic>\n < 0.001), consumption of alcohol (OR\n c<\/jats:sub>\n a<\/jats:sup>\n = 2.893, 95% CI [1.844\u20134.539],\n P<\/jats:italic>\n < 0.001), and salty food intake (OR\n c<\/jats:sub>\n a<\/jats:sup>\n = 4.018, 95% CI [2.538\u20136.362],\n P<\/jats:italic>\n < 0.001) on increasing the GC risk were observed. In addition, no convincing association was found between\n EPHA5<\/jats:italic>\n Pm and the GC prognosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n EPHA5<\/jats:italic>\n methylation in PBLs and its combined effects with environmental risk factors are related to the GC risk.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.7717\/peerj.13774","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T05:25:25Z","timestamp":1663737925000},"page":"e13774","source":"Crossref","is-referenced-by-count":6,"title":["Association between\n EPHA5<\/i>\n methylation status in peripheral blood leukocytes and the risk and prognosis of gastric cancer"],"prefix":"10.7717","volume":"10","author":[{"given":"Xu","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"10.7717\/peerj.13774\/ref-1","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.bbrc.2020.03.120","article-title":"Methylation-mediated silencing of the LIM homeobox 6 (LHX6) gene promotes cell proliferation in human pancreatic cancer","volume":"526","author":"Abudurexiti","year":"2020","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"3","key":"10.7717\/peerj.13774\/ref-2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/ACI.0000000000000634","article-title":"Genetics and epigenetics of allergy","volume":"20","author":"Agache","year":"2020","journal-title":"Current Opinion in Allergy & Clinical Immunology"},{"issue":"4","key":"10.7717\/peerj.13774\/ref-3","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/j.1530-0277.2006.00068.x","article-title":"Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence","volume":"30","author":"Bleich","year":"2006","journal-title":"Alcoholism: Clinical and Experimental Research"},{"issue":"6","key":"10.7717\/peerj.13774\/ref-4","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"2","key":"10.7717\/peerj.13774\/ref-5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10689-020-00201-5","article-title":"Is a colorectal neoplasm diagnosis a trigger to change dietary and other lifestyle habits for persons with Lynch syndrome? 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