{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:42:07Z","timestamp":1782258127288,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,4,24]],"date-time":"2012-04-24T00:00:00Z","timestamp":1335225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The matrix metalloproteinase (MMP) family of proteins mediates various cellular pathways, including apoptosis and angiogenesis. Polymorphisms of <jats:italic>MMP<\/jats:italic> genes are associated with increased esophageal adenocarcinoma (EAC) risk. Gastroesophageal reflux disease (GERD) is an established EAC risk factor. We examined whether <jats:italic>MMP<\/jats:italic> polymorphism\u2010EAC risk is modified by GERD. In total, 309 EAC patients and 279 frequency\u2010matched healthy controls underwent <jats:italic>MMP1 1G\/2G, MMP3 6A\/5A, MMP12<\/jats:italic> \u2212<jats:italic>82A\/G<\/jats:italic> and <jats:italic>MMP12 1082A\/G<\/jats:italic> genotyping. Questionnaires collected GERD history. EAC risk was analyzed using logistic regression, adjusted for key covariates and stratified by GERD. Joint effects models explored GERD severity and duration, whereas additional models explored genotype\u2013GERD interactions in EAC risk. We determined that each <jats:italic>MMP1<\/jats:italic> and <jats:italic>MMP3<\/jats:italic> minor (variant) allele was independently associated with increased EAC risk (adjusted odds ratio (AOR) 3.2, 95% confidence interval (CI) 2.0\u20135.1, <jats:italic>p<\/jats:italic> &lt; 0.001 and AOR 1.8, 95% CI 1.1\u20132.7, <jats:italic>p<\/jats:italic> = 0.01, respectively) only among those with GERD but not in GERD\u2010free individuals (all <jats:italic>p<\/jats:italic> = nonsignificant). There were significant interactions between the <jats:italic>MMP1<\/jats:italic> variants and the presence of GERD (<jats:italic>p<\/jats:italic> = 0.002) and between <jats:italic>MMP3<\/jats:italic> variants and GERD (<jats:italic>p<\/jats:italic> = 0.04). There was an equally strong interaction between cumulative GERD severity and <jats:italic>MMP1<\/jats:italic> (<jats:italic>p<\/jats:italic> = 0.002). The AOR of each variant allele was 14.9 (95% CI 1.6\u2013136) for individuals with severe GERD, 1.7 (95% CI 1.0\u20132.7) for mild\u2010moderate GERD and 0.98 (95% CI 0.7\u20131.4) for those without GERD. This was further reflected in separate analyses of frequency and duration of GERD. In conclusion, <jats:italic>MMP1<\/jats:italic>\n<jats:italic>1G\/2G<\/jats:italic> (and possibly <jats:italic>MMP3 6A\/5A<\/jats:italic>) polymorphisms alter EAC risk differentially for GERD and GERD\u2010free individuals.<\/jats:p>","DOI":"10.1002\/ijc.27541","type":"journal-article","created":{"date-parts":[[2012,3,16]],"date-time":"2012-03-16T07:01:33Z","timestamp":1331881293000},"page":"2478-2486","source":"Crossref","is-referenced-by-count":25,"title":["Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma"],"prefix":"10.1002","volume":"131","author":[{"given":"Winson Y.","family":"Cheung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihong","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Bradbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hopkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew H.","family":"Kulke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca 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C.","family":"Christiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,24]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djn211"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20010801)92:3<549::AID-CNCR1354>3.0.CO;2-L"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-007-9000-1"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21542"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.4065\/83.10.1087"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwm051"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg047"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011290704728"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5402_3"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.15.1972"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc745"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi283"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10750"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-7-187"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh327"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr1033"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199807)185:3<256::AID-PATH115>3.0.CO;2-A"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601372"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i5.676"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2001.1929"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp065"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940611501011"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940411301104"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm020"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4932"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp126"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-04-0612"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh153"},{"key":"e_1_2_5_30_2","first-page":"1377","article-title":"Gene\u2010environmental 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