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Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (<jats:italic>NOS2<\/jats:italic>), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of<jats:italic>NOS2<\/jats:italic>polymorphisms Ser<jats:sup>608<\/jats:sup>Leu (rs2297518) in exon 16, -954G\/C and -1173C\/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and<jats:italic>H. pylori<\/jats:italic>infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed<jats:italic>NOS2<\/jats:italic>genotyping by PCR-RFLP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SNP Ser<jats:sup>608<\/jats:sup>Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p &lt; 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the<jats:italic>NOS2<\/jats:italic>SNP -954G\/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G\/C polymorphism. These findings show that several polymorphisms in the promoter region of the<jats:italic>NOS2<\/jats:italic>gene may contribute to the susceptibility to gastric cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Polymorphism<jats:italic>NOS2<\/jats:italic>-954 G\/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the<jats:italic>NOS2<\/jats:italic>Ser<jats:sup>608<\/jats:sup>Leu polymorphism was not associated with gastric carcinogenesis. The<jats:italic>NOS2<\/jats:italic>-1173C\/T polymorphism was absent in the studied population.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-230x-10-64","type":"journal-article","created":{"date-parts":[[2010,6,18]],"date-time":"2010-06-18T06:13:52Z","timestamp":1276841632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gastric cancer is associated with NOS2-954G\/C polymorphism and environmental factors in a Brazilian population"],"prefix":"10.1186","volume":"10","author":[{"given":"Yvana C","family":"Jorge","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia C","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana E","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,6,17]]},"reference":[{"key":"455_CR1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/978-1-60327-492-0_23","volume":"472","author":"H Brenner","year":"2009","unstructured":"Brenner H, Rothenbacher D, Arndt V: Epidemiology of stomach cancer. 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