{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:53:52Z","timestamp":1770782032245,"version":"3.50.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,8,18]],"date-time":"2004-08-18T00:00:00Z","timestamp":1092787200000},"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":[[2004,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated in a case\u2010control study a possible role of thymidylate synthase gene (<jats:italic>TS<\/jats:italic>) polymorphisms for gastric cancer susceptibility. Lymphocyte genomic DNA from 134 Italian gastric cancer patients and 139 controls was used for genotyping two polymorphisms in the <jats:italic>TS<\/jats:italic> 5\u2032\u2010untranslated region (5\u2032\u2010UTR); a double (2R) or triple (3R) 28\u2010bp repeat and a G\/C polymorphism within the triple repeats allele (3G allele). Samples were also genotyped at a 6\u2010bp deletion\/insertion (del6 or ins6) polymorphism at position 1494 in the <jats:italic>TS<\/jats:italic> 3\u2032\u2010untranslated region (3\u2032\u2010UTR). Unconditional regression with odd ratios (OR) and 95% confidence intervals (CI), haplotype and linkage disequilibrium analyses were used to investigate the association of the polymorphisms with the disease. The global allelic distribution was in Hardy\u2010Weinberg equilibrium. Genotypes with the 3G allele (2R\/3G, 3C\/3G, 3G\/3G) were significantly more frequent in patients than controls and were associated with gastric cancer risk (OR = 2.06; 95% CI = 1.26\u20133.35). A significant risk was also observed for carriers of the del6 allele in the 3\u2032\u2010UTR. Odds ratios for combined 3G\u2010del6\/ins6 and 3G\u2010del6\/del6 genotypes were 2.59 (95% CI = 1.36\u20134.94) and 2.81 (95% CI = 1.22\u20136.64), respectively. The 3G\u2010del6 haplotype showed a significant association with the disease (<jats:italic>p<\/jats:italic> = 0.01). Polymorphisms in the <jats:italic>TS<\/jats:italic> gene may contribute to gastric cancer susceptibility and this finding deserve further investigation in the context of novel strategies for gastric cancer prevention. <jats:italic>In vitro<\/jats:italic>, 3G genotypes have been related to high <jats:italic>TS<\/jats:italic> mRNA expression, which may underlie one of the possible etiologic mechanisms. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20489","type":"journal-article","created":{"date-parts":[[2004,8,19]],"date-time":"2004-08-19T16:17:05Z","timestamp":1092932225000},"page":"1010-1014","source":"Crossref","is-referenced-by-count":38,"title":["Association of thymidylate synthase polymorphisms with gastric cancer susceptibility"],"prefix":"10.1002","volume":"112","author":[{"given":"Francesco","family":"Graziano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Go","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Ruzzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bostjan","family":"Humar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Catalano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Ficarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Merriman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Panunzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Testa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Cascinu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Italo","family":"Bearzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Tonini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Magnani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,8,18]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.49.1.33"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/srao.2002.30815"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10466"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570160043377628"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500012"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11641"},{"key":"e_1_2_6_8_2","first-page":"958","article-title":"Polymorphism in the thymidylate synthase promoter enhancer region modifies the risk and survival of colorectal cancer","volume":"12","author":"Chen J","year":"2003","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_6_9_2","first-page":"A2614","article-title":"Alterations of the thymidylate synthase (TS) pathway and colorectal cancer risk. 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