Helicobacter pylori (H. pylori) is a spiral-shaped, Gram negative, microaerophilic bacterium, and is classified as a group I carcinogen by the World Health Organization’s International Agency in 1994. Infection of H. pylori is associated with several gastrointestinal diseases including acute and chronic gastritis, atrophic gastritis, gastric ulcer, duodenal ulcer, and gastric adenocarcinoma. H. pylori virulence determinants, host factors, and environmental influences are considered to contribute to the differential clinical sequelae of the infection. Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to influence gene expression, and are linked to increased susceptibility to certain infectious and autoimmune diseases. The genetic polymorphisms of pro-inflammatory cytokines are associated with the level of inflammation in H. pylori-infected patients and increased gastric cancer risk. T regulatory cells (Tregs) are a small population of T lymphocytes that may induce and maintain immunologic self-tolerance to prevent the development of autoimmune diseases. Increased Tregs are associated with various types of cancers including gastric cancer, and suppress anti-tumor immunity. In addition, Tregs reduce proinflammatory cytokine production by suppressing H. pylori–induced T cell responses.
In the first part of this work, we focus on the cytokine SNPs and its association with reflux esophagitis, gastritis, gastric ulcer, and duodenal ulcer. Polymorphisms of interleukin 1□ (IL-1□), IL-8, IL-10 and tumor necrosis factor □ (TNF-□) were determined by using the polymerase chain reaction□restriction fragment length polymorphism (PCR□RFLP) method in 804 subjects from Taichung Veterans General Hospital. The results showed that IL-1□□polymorphisms were associated with an increased risk of erosive reflux esophagitis and IL-10 polymorphisms were associated with an increased risk of gastritis.
In the second part, we focus on the numbers of T regulatory cells and its association with gastritis, peptic ulcer, and gastric adenocarcinoma. CD4+, CD25+, and Foxp3+ cells in antral gastric mucosa of 167 subjects from Ton-Yen General Hospital were determined by immunohistochemistry in three consecutive paraffin-embedded serial sections of gastric biopsies sections per sample. The results showed that Tregs was positively associated with endoscopic findings of gastroduodenal diseases and histological grade but was negatively associated with intestinal metaplasia in gastritis and peptic ulcers.
Therefore, we suggested that IL-1□ high-producer SNPs promote GERD risk, IL-10 high-producer SNPs promote gastritis risk, and IL-10 play an important role in gastric cancer progression. Tregs were important in H. pylori infection and progression of gastric cancer.

幽門螺旋菌是一種外型呈現螺旋型並為革蘭性陰性之微需氧細菌，在1994年已經被世界衛生組織確認具有致癌風險。幽門螺旋菌的感染與不同的胃腸道疾病有關，像是急性胃炎、慢性胃炎、萎縮型胃炎、胃潰瘍、十二指腸潰瘍、甚至是胃癌。胃幽門螺旋菌的致命因子被認為是造成疾病的原因。幽門螺旋菌之毒性因子、宿主因子及環境的影響被認為是感染病症的因素。細胞激素單核苷酸多型性已被證實會影響基因表現，並會增加某些感染性疾病及自體免疫疾病的感受性。前驅發炎細胞激素的基因多型性與感染幽門螺旋菌病人的發炎程度有關，並且會增加胃癌的發生率。調控型T細胞是T淋巴細胞群中的一小部分，可能誘發和維持自體免疫耐受性而防止自體免疫疾病的發展。增加的調控型T細胞與不同類型的癌症有相關性，包括胃癌，並能抑制抗腫瘤的免疫反應。此外，調控型T細胞藉由抑制幽門螺旋菌誘發的T細胞反應降低前驅發炎細胞激素的表現。
在第一部分的研究中，我們首先探討細胞激素單核苷酸多型性與食道逆流、胃發炎、胃潰瘍及十二指腸潰瘍的相關性研究。我們利用限制酶連鎖反應□限制片段長度多型性分析在來自台中榮民總醫院的804位病人中介白素-1□、介白素8、介白素10以及腫瘤壞死因子-□的基因多型性。結果顯示介白素-1□單核苷酸多型性與食道逆流相關，而介白素10則與胃炎相關。
在第二部份，我們接著探討調控型T細胞數與胃發炎、消化性潰瘍及胃癌的相關性研究。我們利用免疫組織染色法在來自竹北東元醫院167個病人之石蠟包埋胃幽門黏膜組織的三個連續切片中觀察CD4+、CD25+、和Foxp3+表現的細胞個數。結果顯示調控型T細胞與腸胃道疾病的內視鏡結果以及組織學分級具有正相關性，而與胃炎和消化性潰瘍的腸化生症狀呈現負相關性。
我們認為介白素-1□高表現基因多樣性促進GERD的發生率，介白素10高表現基因多型性促進胃炎的發生率，IL-10在胃癌病變中扮演很重要的角色。胃幽門螺旋菌的感染會造成調控型T細胞增加並參與胃癌病變。

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