IL-1基因多态性与H.pylori感染和汉族人胃黏膜萎缩关系的研究

目的:探讨IL-1B-511基因多态性对幽门螺旋杆菌(Helicobacter pylori,H．pylori)感染后胃黏膜萎缩的影响。方法:1)采用PCR-限制性长度片段多态性(restriction fragment length polymorphism,RFLP)分析法检测胃癌低发区湖北省普通人群192例和胃癌高发区陕西省普通人群169例的基因型。2)采用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测上述人群的H．pylori感染率、胃蛋白酶原Ⅰ(PepsinogenⅠ,PGⅠ)、胃蛋白酶原Ⅱ(PepsinogenⅡ, PGⅡ)和胃泌素(Gastrin)的浓度。结果:1)在胃癌高、低发区,H．pylori阳性者PGⅠ／PGⅡ显著低于H．pylori阴性者,胃癌高发区H．pylori阳性者PGⅠ／PGⅡ显著低于胃癌低发区的H．pylori阳性者(P=0．003和P＝0．002)。2)在胃癌低发区,H．pylori阳性的IL-1B-511T／T基因型者PGⅠ／PGⅡ显著低于C／C和T／T基因型者(P=0．032和P=0．034),而胃癌高发区,IL-1B-511T／T基因型人群PGⅠ／PGⅡ又显著低于低发区相应人群(P=0．036),但与高发区IL-1B-511C／T和C／C基因型者一致。IL-1B-511各基因型者的血清胃泌素浓度之间差异无统计学意义。结论:在胃癌高、低发区,IL-1B-511T／T基因型可能增加感染H．pylori后中国汉族人群胃黏膜萎缩发生发展的危险性;胃癌高发区,中国汉族人群胃黏膜萎缩的发生发展除与H．pylori感染和遗传有关外,环境因素可能起相当重要的作用。     

IL-1B基因多态性与胃癌易感相关性研究

目的:探讨河南地区汉族人白细胞介素(IL)-1B基因多态性与胃癌的相关性以及是否与胃癌组织学分型相关联.方法: 采用聚合酶链反应-单链构象多态性技术(PCR-SSCP)和琼脂糖凝胶电泳(AGE)检测了220例对照和452例胃癌患者(肠型176例,弥散型137例,萎缩型139例)的IL-1B-511C/T基因位点.结果: IL-1B-511C等位基因频率在正常人群和胃癌组患者分别为0.82和0.76,IL-1B-511T 等位基因频率分别为0.18和0.24,两者差异有统计学意义.IL-1B-511T纯合子、携带者患肠型胃癌风险的OR分别为2.7(95% CI:1.5～4.9)和3.1(95% CI:1.5～6.5);T等位基因与肠型胃癌易感密切关联,与萎缩型胃癌易感差异无统计学意义,P＞0.05.结论: IL-1B-511C/T基因多态性与胃癌发生风险密切关联,T等位基因可能是肠型胃癌的易感标志.     

白细胞介素-1B 基因多态性、幽门螺杆菌感染与胃癌发生的相关性

 目的 探讨湖南衡阳地区白细胞介素-1B（IL-1B）基因多态性与胃癌的关系以及幽门螺杆菌（Helicobacter pylori,HP）感染后胃癌发生的易感基因型。方法 52例胃癌患者癌旁正常胃粘膜组织和55例慢性胃炎患者胃粘膜组织,均经快速尿素酶和PCR检测HP,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术,进行基因型检测,并对C/C、T/T进行测序,比较各基因型在胃癌组和胃炎组中的分布差异。结果 IL-1B-31T、IL-1B-511T等位基因和IL-1B-31T/T、IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为1.97（95%CI=1.15-3.59）、2.52（95%CI=1.45-4.39）和2.71（95%CI=1.10-6.66）、3.33（95%CI=1.14-9.73）。在伴有HP感染的群体中进行比较,IL-1B-31位点各基因型未见明显差异;但IL-1B-511T等位基因和IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为2.16（95%CI=1.10-4.23）和3.43（95%CI=1.01-11.62）。结论 在湖南衡阳地区IL-1B-31T/T、IL-1B-511T/T基因型与胃癌发病风险相关,在HP被感染后IL-1B-511T/T基因型可能为湖南衡阳地区胃癌易感基因型。     

IL-1B基因多态性与胃癌易感相关性研究IL-1B基因多态性与胃癌易感相关性研究

目的：探讨河南地区汉族人白细胞介素（IL）-1B基因多态性与胃癌的相关性以及是否与胃癌组织学分型相关联.方法： 采用聚合酶链反应-单链构象多态性技术（PCR-SSCP）和琼脂糖凝胶电泳（AGE）检测了220例对照和452例胃癌患者（肠型176例,弥散型 137例,萎缩型139例）的IL-1B-511C/T基因位点.结果： IL-1B-511C等位基因频率在正常人群和胃癌组患者分别为0.82和0.76,IL-1B-511T 等位基因频率分别为0.18和0.24,两者差异有统计学意义.IL-1B-511T纯合子、携带者患肠型胃癌风险的OR分别为2.7（95% CI：1.5～4.9）和3.1（95% CI：1.5～6.5）;T等位基因与肠型胃癌易感密切关联,与萎缩型胃癌易感差异无统计学意义,P＞0.05.结论： IL-1B-511C/T基因多态性与胃癌发生风险密切关联,T等位基因可能是肠型胃癌的易感标志.     

IL-1B基因多态性对胃黏膜组织中IL-1β表达的影响

目的:探讨IL-1B基因多态性影响幽门螺旋杆菌(helicobacter pylori,H.pylori或Hp)感染后胃黏膜IL-1β的表达。方法:采用PCR-限制性长度片段多态性(restriction frag-ment length polymorphism,RFLP)分析法检测胃癌低发区117名普通人群IL-1基因多态性。同时比较不同基因型普通人胃黏膜H.pylori阳性和阴性者的IL-1β表达的差异。结果:在胃窦组织中,H.pylori阴性个体的IL-1βmRNA的表达量极少,而H.pylori阳性个体有明显的表达;但在IL-1B-511T/T、C/C和C/T基因型之间差异无统计学意义,P=0·066。在胃体组织中,H.pylori阴性者IL-1βmRNA无明显表达;而在H.pylori阳性者中,IL-1βmRNA表达显著增加(0·44±0·11和0·76±0·14,t=3·2,P=0·02)。而且H.pylori阳性IL-1B-511T/T基因型个体IL-1βmRNA表达比C/T和C/C基因型明显增加(分别为0·86±0·15、0·70±0·16和0·67±0·16,q=2·4和2·7,P=0·043和0·036)。结论:IL-1B基因多态性(-511位点)可促进H.pylori感染后胃体黏膜IL-1βmRNA的表达。肿瘤防治杂志,2005,12(19):1449-1452     

IL-1B基因多态性和H.pylori感染与胃癌关系的研究

目的:通过比较胃癌低发区广东省胃癌患者与匹配人群的幽门螺旋杆菌(Helicobacterpylori,H.pylori)感染率和IL-1B-31基因多态性,探讨IL-1B-31基因多态性是否增加H.pylori感染后胃癌发生的危险性。方法:1)采用PCR-限制性片段长度多态性(restrictionfragmentlengthpolymorphism,RFLP)分析法检测胃癌低发区广东省84例胃癌患者和84例与之性别、年龄匹配的普通人群的lL-1B-31基因多态性。2)采用酶联免疫吸附法(enzyme-linkedimmunosorbentassay,ELISA)检测上述人群的H.pylori感染率。结果:1)IL-1B-31T/T基因型频率在对照人群与胃癌患者两组间差异无统计学意义,(3·6%vs1·2%,χ2=1·0,P=0·3)。2)84例胃癌患者的H.pylori感染率显著高于对照人群,81·0%vs59·5%,χ2=9·2,P=0·002,OR=2·9。结论:在胃癌低发区广东省,H.py-lori感染是胃癌发生的危险因素,OR=2·9;IL-1B-31T/T基因型不是通过影响HP感染后发生胃癌的危险性,是通过遗传或其他途径增加胃癌发病的危险性。     

IL-1基因多态性对胃粘膜TNF-α、NF-κB的表达和活性的影响

 目的 探讨IL-1的基因多态性影响H.pylori感染后胃癌发生的机制。 方法 通过多态性分析和血清H.pylori抗体测定,收集105例癌低发区的学生作为研究对象,其中IL-1-511T/T 基因型32名（13名H.pylori+）,C/C基因型36名（15名H.pylori+）,C/T基因型37名（14名H.pylori+）。 结果 在胃体组织,H.pylori阴性个体TNF-α和NF-κB表达量极少,而且IL- 1B-511各基因型间也无显著差异。在H.pylori阳性个体,胃体部TNF-α和NF-κB mRNA有较为明显的表达,IL-1B-511T/T基因型个体比C/T和C/C基因型明显增加,分别为1.20±0.17 vs. 0.87±0.18和0.94±0.16;1.10±0.16 vs 0.90±0.15和0.97±0.17,F=33.4和12.9,P=0.0001和0.001。H.pylori阴性的NF-κB mRNA活性很低。在H.pylori阳性个体,NF-κB 活性显著增加。而且IL-1B-511T/T基因型个体比C/T和C/C基因型明显增加,分别为0.99±0.12vs 0.89±0.15和0.90±0.14,F=5.6,P=0.005。 结论 H.pylori感染促进TNF-α和NF-κ B mRNA表达,上调NF-κB活性,在IL-1B-511T/T基因型个体更明显。提示H.pylori感染后,存在IL-1B基因多态性→IL-1β↑→炎症细胞因子↑→胃癌发生的完整通路。     

中国人群IL-1基因多态性与胃癌发生易感性Meta分析

目的:探讨中国人群IL-1基因多态性与胃癌发生的相关性.方法:通过检索MEDLINE、Embase、Cancerlit、AACR(American association for cancer re-search)、中国生物医学文献数据库(CBM-disc)、中国知网、万方数据库等数据库,纳入16个关于IL-1-31,IL-1B-511,和IL-1RN基因多态性和胃癌相关性的病例对照研究.采用RevMan 4.2.2统计软件进行文献的异质性检验并计算合并效应优势比(OR)和95%可信区间(CI).结果:经筛选纳入16个病例一对照研究,其中包舍2 099例胃癌病例和2 371个正常对照,IL-1B-31C,IL-1B-511T和IL-1 RN 3个位点的OR和C1分剐是[0R=0.98,95%CI(0.72～1.34);P=0.89]、[0R=1.45,95%CI(1.00～2.09);P=0.05]、[0R=1.61,95%CI(0.97～2.67);P=0.07].结论:在中国人群中,IL-1B-31和IL-1RN两位点基因多态性与胃癌发生不存在关联性,IL-1B-511位点基因多态性与胃癌发生易感性相关联.     

IL-1β基因多态性、幽门螺旋杆菌感染及其交互作用与新疆汉族胃癌发生的关系

目的探讨IL-1β基因多态性、幽门螺旋杆菌(Helicobacter pylori,HP)感染及其交互作用与新疆汉族胃癌发生的关系。方法采用Snapshot技术分析229例胃癌患者和作为对照的256例非胃癌患者IL-1β基因rs1143633、rs3136558和rs1143630位点基因型的分布;采用幽门螺旋杆菌IgG抗体检测试剂盒检测研究对象Hp感染率。结果IL-1β基因rs3136558位点多态性、Hp感染与新疆汉族胃癌的发病有关;Hp感染与基因之间的交互作用表明,在汉族人群中,Hp感染阳性,同时携带IL-1β基因 rs3136558 TT基因型个体发生胃癌的危险性是Hp感染阴性并携带IL-1β基因 rs3136558 CT+CC基因型个体的2.25倍 (95% CI：1.37~3.69)。结论Hp感染和IL-1β基因多态之间存在着交互作用,共同促进胃癌的发生。     

炎症相关基因多态性与子宫颈癌发病风险及治疗疗效的关系

目的 分析炎症相关基因多态性与子宫颈癌发病风险及治疗疗效的关系.方法 选取110例子宫颈癌患者作为实验组,另选取110例同期体检健康者作为对照组,分析IL-1B、IL-1RN及TNF-α等炎症相关基因的多态性,并比较其与子宫颈癌的发病风险及其治疗疗效的相关性.结果 携带IL-1B-511TT基因型、IL-1B-511CT基因型及IL-1B-511CT/TT基因型的患者发生子宫颈癌的风险较高(P<0.05);携带TNF-α-G/A基因型者子宫颈癌发病率较高(P<0.05);而携带IL-1RN变异型基因1/2与2/2的患者子宫颈癌发生率相对较低(P>0.05),以上基因多态性与子宫颈癌患者的临床疗效无明显相关性.结论 IL-1B-511TT、IL-1B-511CT、IL-1B-511CT/TT及TNF-α-G/A等炎症相关基因的多态性可能提高子宫颈癌的发病率,而IL-1RN变异型基因1/2与2/2可能会降低子宫颈癌的发病率,炎症相关基因多态性与子宫颈癌的临床治疗效果不相关.     

Interleukin 1B gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in Helicobacter pylori-negative gastric cancer of intestinal and diffuse histotype.

BACKGROUND: Polymorphisms in the interleukin 1beta gene (IL-1B-31T/C and IL-1B-511C/T single nucleotide changes) and in the interleukin 1 receptor anatagonist gene (IL-1RN2 variable number of tandem repeats) have been studied with respect to gastric cancer susceptibility. Available data support an aetiologic role of these genetic variants in the presence of concomitant Helicobacter pylori infection. Their contribution without H. pylori infection is still an open field of investigation. MATERIALS AND METHODS: IL-1B and IL-1RN polymorphisms were investigated in 138 H. pylori-negative Italian patients with sporadic gastric cancer and 100 H. pylori-negative controls. 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 disease. RESULTS: In all gastric cancer cases, carriers of the homozygous IL-1B-511T/T genotype showed a significant risk for the development of the disease (OR 3.2 with 95% CI 1.27-8.05). In cases with intestinal-type gastric cancer, however, both IL-1B-511T and IL-1RN2 alleles were associated with disease. In this subgroup, the odds ratio for carriers of both IL-1B-511T and IL-1RN2 was 6.49 (95% CI 2.07-20.4). Haplotype analysis supported the aetiologic contribution of these alleles in gastric cancer of the intestinal histotype. CONCLUSIONS: In conclusion, IL-1B-511T and IL-1RN2 may contribute to intestinal gastric cancer risk in the absence of concomitant H. pylori infection. In this setting, future epidemiologic studies should consider dietary habits and exposure to carcinogens interacting with pro-inflammatory host genotypes.     

Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer.

PURPOSE: A high interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-RN) ratio underlies an unfavorable proinflammatory status. Also, it seems to be involved in the mechanisms of cancer cachexia and tumor angiogenesis and metastasis. Two single nucleotide polymorphisms in IL-1B gene (IL-1B-511C/T,IL-1B-31T/C) and a variable number of tandem repeat polymorphisms in IL-RN gene (IL-1RNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/IL-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy. PATIENTS AND METHODS: Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-1RN/IL-1B genotypes. RESULTS: Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-1B-31T/T; group A). Forty-five patients showed the IL-1RN2 polymorphism, with wild-type IL-1B genotypes in seven patients and with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms in 38 patients (group B). The remaining 36 patients demonstrated wild-type IL-1RN, with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms (group C). In group A and B patients, the median progression-free survival (PFS) was 25 and 26 weeks, respectively, and median overall survival (OS) was 42 and 43 weeks, respectively. Group C patients showed worse PFS (median, 16 weeks) and OS (median, 28 weeks) than group A (P = .006 for PFS; P = .0001 for OS) and group B patients (P = .01 for PFS; P = .0001 for OS). The long/T/C haplotype was overrepresented in patients with shortened PFS (P = .001) and OS (P = .0005). CONCLUSION: In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-1RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN.     

Interleukin-1beta gene in esophageal, gastric and colorectal carcinomas

Interleukin (IL)-1 gene polymorphisms are associated with development of gastric atrophy and with increased risk of gastric carcinoma. A -31C to T base transition in the promoter region of this gene is involved in carcinogenic changes within the stomach, especially in Helicobacter pylori infected individuals. We examined association between IL-1 locus polymorphisms and risk of esophageal, gastric and colorectal carcinomas in Japanese patients with H. pylori infection. IL-1B and IL-1RN polymorphisms were analyzed in 136 controls, 75 patients with esophageal carcinoma, 186 patients with gastric carcinoma, 69 patients with colorectal carcinoma, and 18 patients with ulcerative colitis (UC). For IL-1B-511 and -31 polymorphisms were determined by fluorescence-based polymerase chain reaction single-strand conformation polymorphism analysis. For IL-1 receptor antagonist gene (IL-1RN), penta-allelic variable number of tandem repeats (VNTR) was determined by PCR-standard agarose gel electrophoresis. For gastric carcinoma, IL-1B-511 heterozygotes (OR, 0.48; 95% CI, 0.3-0.9; p=0.0115) and T carriers (OR, 0.52; 95% CI, 0.3-1.0; p=0.0185) had a significantly reduced risk of carcinoma. For colorectal carcinoma, IL-1B-511 heterozygotes (OR, 0.34; 95% CI, 0.2-0.7; p=0.0028) and T carriers (OR, 0.43; 95% CI, 0.2-0.9; p=0.0015) had a significantly low risk of carcinoma. No significant difference was observed in the frequencies of IL-1B-31C/T and IL-1RN genotypes between controls and the esophageal carcinoma patients. Our results shows that IL-1B-511C/T and T carrier state may indicate less risk for gastric and colorectal carcinoma in the Japanese population.     

Serum pepsinogen levels in gastric cancer patients and their relationship with Helicobacter pylori infection: a prospective study.

BACKGROUND: Our aim was to study the serum pepsinogen levels in gastric cancer patients in our population in relation to histology and the presence of Helicobacter pylori. METHODS: Forty-six patients with gastric cancer and 70 controls were studied prospectively in a 1-year period. Serum levels of pepsinogen I (PG I), pepsinogen II (PG II), and gastrin were measured by radioimmunoassay. RESULTS: The mean PG I levels for cancer patients and controls were 83.5 microg/l and 60.9 microg/l, respectively (P = 0.03), the mean PG II levels were 27.2 microg/l and 12.1 microg/l respectively (P < 0.0001). The PG I/II ratio was significantly lower in cancer patients (P = 0.04) and in those with Helicobacter infection. Serum pepsinogen levels were not affected by any pathological characteristics. Histology showed that the prevalence of chronic gastritis, intestinal metaplasia, and gastric atrophy was 97%, 56%, and 15%, respectively. CONCLUSION: The prevalence of gastric atrophy is low in our population, and serum pepsinogen measurement is not useful as a screening tool for gastric cancer in this population.     

Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma

BACKGROUND: Both Helicobacter pylori genotype and host genetic polymorphisms play a role in determining the clinical consequences of H. pylori infection. We investigated whether there are any combinations of bacterial and host genotypes that are particularly associated with the occurrence of gastric carcinoma. METHODS: Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay. Polymorphisms in the human interleukin 1 beta (IL-1B) gene (IL-1B-511*C or IL-1B-511*T) and in the IL-1 receptor antagonist gene (IL-1RN intron 2 variable number of tandem repeats) were evaluated by PCR and single-strand conformation polymorphism analysis. All statistical tests were two-sided. RESULTS: Infection with vacAs1-, vacAm1-, and cagA-positive strains of H. pylori was associated with an increased risk for gastric carcinoma, with odds ratios (ORs) of 17 (95% confidence interval [CI] = 7.8 to 38), 6.7 (95% CI = 3.6 to 12), and 15 (95% CI = 7.4 to 29), respectively. IL-1B-511*T carriers (IL-1B-511*T/*T or IL-1B-511*T/*C) homozygous for the short allele of IL-1RN (IL-1RN*2/*2) had an increased gastric carcinoma risk (OR = 3.3, 95% CI = 1.3 to 8.2). For each combination of bacterial/host genotype, the odds of having gastric carcinoma were greatest in those with both bacterial and host high-risk genotypes: vacAs1/IL-1B-511*T carrier (OR = 87, 95% CI = 11 to 679), vacAm1/IL-1B-511*T carrier (OR = 7.4, 95% CI = 3.2 to 17), cagA-positive/IL-1B-511*T carrier (OR = 25, 95% CI = 8.2 to 77), vacAs1/IL-1RN*2/*2 (OR = 32, 95% CI = 7.8 to 134), vacAm1/IL-1RN*2/*2 (OR = 8.8, 95% CI = 2.2 to 35), and cagA-positive/IL-1RN*2/*2 (OR = 23, 95% CI = 7.0 to 72). CONCLUSION: Combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.     

Interleukin-1B (IL-1B) polymorphisms and gastric mucosal levels of IL-1beta cytokine in Korean patients with gastric cancer

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1beta and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1beta cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1beta levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1beta production contributed to the development of intestinal-type GC in this Korean population.