胃癌与巴西人群中 NOS2-954G/C 多态性和环境因素有关。
Gastric cancer is associated with NOS2 -954G/C polymorphism and environmental factors in a Brazilian population.
机构信息
Department of Biology,UNESP, São Paulo State University, SP, Brazil.
出版信息
BMC Gastroenterol. 2010 Jun 17;10:64. doi: 10.1186/1471-230X-10-64.
BACKGROUND
Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from Helicobacter pylori infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (NOS2), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of NOS2 polymorphisms Ser608Leu (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 H. pylori infection.
METHODS
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 NOS2 genotyping by PCR-RFLP.
RESULTS
SNP Ser608Leu 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 < 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 NOS2 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 NOS2 gene may contribute to the susceptibility to gastric cancer.
CONCLUSIONS
Polymorphism NOS2 -954 G/C, along with alcohol intake and tobacco smoking, is associated with gastric cancer. However, the NOS2 Ser608Leu polymorphism was not associated with gastric carcinogenesis. The NOS2 -1173C/T polymorphism was absent in the studied population.
背景
胃癌可由幽门螺杆菌感染引起的胃黏膜慢性炎症发展而来，该感染可激活宿主的炎症反应。因此，参与炎症反应的基因（如诱导型一氧化氮合酶（NOS2））中的多态性与胃癌的发生有关。本研究旨在评估 NOS2 基因 16 号外显子 Ser608Leu（rs2297518）、启动子区 -954G/C 和 -1173C/T 多态性与胃癌和慢性胃炎的关系，并探讨癌症与吸烟、饮酒和 H. pylori 感染等危险因素的关系。
方法
我们在 474 名巴西东南部人群中进行了一项基于人群的病例对照研究（150 名胃癌患者、160 名慢性胃炎患者和 164 名健康对照者），通过 PCR-RFLP 进行 NOS2 基因分型。
结果
SNP Ser608Leu 与慢性胃炎或胃癌的风险无关。在所研究的人群中未发现多态性等位基因-1173T。然而，-954GC+CC 基因型的频率在癌症组（48.7%）显著高于胃炎组（28.1%）和对照组（29.9%）（p<0.01）。多因素 logistic 回归显示，NOS2 SNP-954G/C 与胃癌风险增加相关（OR=1.87；95%CI=1.12-3.13）。我们还观察到该 SNP 与吸烟和饮酒等危险因素相关，无论是在胃癌（OR=2.68；95%CI=1.58-4.53；OR=3.60；95%CI=2.05-6.32）还是慢性胃炎（OR=1.93；95%CI=1.19-3.13；OR=2.79；95%CI=1.55-5.02）组中均如此。这是首次报道-954G/C 多态性与胃癌风险增加相关。这些发现表明，NOS2 基因启动子区的多个多态性可能导致胃癌易感性增加。
结论
NOS2-954G/C 多态性与酒精摄入和吸烟共同与胃癌相关。然而，NOS2 Ser608Leu 多态性与胃癌发生无关。在所研究的人群中，NOS2-1173C/T 多态性不存在。
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