{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:39:50Z","timestamp":1790393990684,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T00:00:00Z","timestamp":1369440000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The role of tumor suppressor gene <jats:italic>RASSF1A<\/jats:italic> in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of <jats:italic>RASSF1A<\/jats:italic> were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We firstly analyzed the prevalence of <jats:italic>RASSF1A<\/jats:italic> A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the <jats:italic>RASSF1A<\/jats:italic> in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The frequency of 133Ala\/Se and Ser\/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, <jats:italic>P<\/jats:italic>=0.02). Compared with Ala\/Ala genotype, Ala\/Se and Ser\/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09\u20133.97). However, this polymorphism had no association with ESCC (<jats:italic>P<\/jats:italic>=0.69). The promoter methylation of <jats:italic>RASSF1A<\/jats:italic> gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78\u201312.52) and GCA (OR=7.50, 95% CI= 2.78\u201320.23). Promoter methylation of <jats:italic>RASSF1A<\/jats:italic> gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10\u20138.73; for differentiation: OR=0.29, 95% CI=0.12\u20130.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03\u20130.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57\u2013167.74).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The present findings suggest that alterations of <jats:italic>RASSF1A<\/jats:italic> may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, <jats:italic>RASSF1A<\/jats:italic> hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2407-13-259","type":"journal-article","created":{"date-parts":[[2013,5,25]],"date-time":"2013-05-25T22:14:22Z","timestamp":1369520062000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Polymorphism of A133S and promoter hypermethylation in Ras association domain family 1A gene (RASSF1A) is associated with risk of esophageal and gastric cardia cancers in Chinese population from high incidence area in northern China"],"prefix":"10.1186","volume":"13","author":[{"given":"Sheng Li","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong Min","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Min","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Chi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue Ke","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze Chen","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Xing","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,5,25]]},"reference":[{"key":"3891_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3322\/caac.20107","volume":"61","author":"A Jemal","year":"2011","unstructured":"Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. 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