{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T12:26:41Z","timestamp":1775305601789,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,4,3]],"date-time":"2008-04-03T00:00:00Z","timestamp":1207180800000},"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":[[2008,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rates of adenocarcinoma of the esophagus (EAC) and esophago\u2010gastric junction (EGJAC) have increased rapidly in recent decades. The primary risk factors, gastro\u2010esophageal acid reflux and smoking, are potentially genotoxic through the generation of <jats:italic>N<\/jats:italic>\u2010nitroso compounds. The DNA repair protein O<jats:sup>6<\/jats:sup>\u2010methylguanine\u2010DNA methyltransferase (MGMT) is the major cellular defense against alkylating DNA damage. We compared patients with EAC (<jats:italic>n<\/jats:italic> = 263) or EGJAC (<jats:italic>n<\/jats:italic> = 303) with matched population controls (<jats:italic>n<\/jats:italic> = 1,337) for the frequency of 5 <jats:italic>MGMT<\/jats:italic> single nucleotide polymorphisms (SNPs) (rs12269324, rs12268840, L84F, I143V, K178R), as well as SNPs in DNA repair genes <jats:italic>ERCC1<\/jats:italic> (N118N), <jats:italic>XRCC1<\/jats:italic> (Q399R) and <jats:italic>XPD<\/jats:italic> (K751Q). Relative risks were estimated using multivariable logistic regression. Potential biological interaction was assessed through the synergy index <jats:italic>S<\/jats:italic>. Each <jats:italic>MGMT<\/jats:italic> SNP conferred increased risks of EAC but not EGJAC; strongest associations were found for the 2 variant <jats:italic>MGMT<\/jats:italic> alleles rs12268840 and I143V (<jats:italic>p<\/jats:italic> = 0.005 and <jats:italic>p<\/jats:italic> &lt; 0.001, respectively). Homozygous carriers of <jats:italic>MGMT<\/jats:italic> rs12268840 with frequent acid reflux had significantly higher risks of EAC (OR 15.5, 95% CI 5.8\u201342) than expected under an additive model, consistent with biological interaction (<jats:italic>S<\/jats:italic> = 3.3, 95% CI 1.1\u201310). Modest, nonsignificant interactions with smoking were also observed. Homozygous variant <jats:italic>ERCC1<\/jats:italic> genotype was associated with reduced risks of EAC (OR 0.6, 95% CI 0.4\u20131.1), while the homozygous variant <jats:italic>XRCC1<\/jats:italic> genotype conferred higher risks of EGJAC (OR 1.6, 95% CI 1.1\u20132.4). No associations with EAC or EGJAC were observed with <jats:italic>XPD<\/jats:italic> (rs13181). In summary, <jats:italic>MGMT<\/jats:italic> SNPs are associated with increased risks of EAC. Exposure to acid reflux, and possibly smoking, confer markedly higher risks among homozygous variant genotype carriers. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23410","type":"journal-article","created":{"date-parts":[[2008,4,3]],"date-time":"2008-04-03T13:19:50Z","timestamp":1207228790000},"page":"174-180","source":"Crossref","is-referenced-by-count":57,"title":["Polymorphisms in MGMT and DNA repair genes and the risk of esophageal adenocarcinoma"],"prefix":"10.1002","volume":"123","author":[{"given":"James","family":"Doecke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen Zhen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirmala","family":"Pandeya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Sadeghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell","family":"Stark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ad\u00e8le C.","family":"Green","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas K.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope M.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David C.","family":"Whiteman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the Australian Cancer Study","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,4,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1991.03460100089030"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1998.tb00646.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013756531219"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji024"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530060048032"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903183401101"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.047126"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.066043"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32963"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.8.1095"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005948420548"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(99)00014-7"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc824"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.03.008"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2007.03.012"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi087"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970529)71:5<719::AID-IJC5>3.0.CO;2-U"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0437"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9078"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl160"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi115"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl017"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm020"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.131375"},{"key":"e_1_2_6_26_2","volume-title":"Pathology and genetics. 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