Serviço de Higiene e Epidemiologia, Faculdade de Medicina da Universidade do Porto, Al. Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):762-76. doi: 10.1158/1055-9965.EPI-09-0917. Epub 2010 Mar 3.
Polymorphisms within interleukin-1 (IL1) and tumor necrosis factor alpha (TNFA) gene clusters are associated with an increased risk of gastric cancer. However, their role in gastric precancerous lesions remains poorly understood. Our objective was to perform a meta-analysis of studies addressing the association between IL1B-511, IL1RN variable number of tandem repeat, and TNFA-308 gene polymorphisms and gastric precancerous lesions, including original data from Portugal and Mozambique. Published studies on the association between these cytokine gene polymorphisms and gastric precancerous lesions were identified by systematic review, and estimates of the association were combined using random-effects meta-analysis taking into account new data obtained from Portuguese volunteer shipyard workers (n = 215) and Mozambican dyspeptic patients (n = 96) who underwent endoscopic and pathologic evaluation following the same protocol. Odds ratio (OR) estimates for intestinal metaplasia were 2.83 [95% confidence interval (95% CI), 1.15-6.96] for the IL1RN22 genotype, 1.86 (95% CI, 1.03-3.36) for IL1B-511 T carriers, and 0.59 (95% CI, 0.12-3.04) for the TNFA-308AA genotype in the Portuguese sample. All Mozambican subjects with intestinal metaplasia were T carriers for IL1B-511 and none had the 2 allele for IL1RN. In meta-analysis, IL1RN22 genotype was associated with an increased risk of gastric precancerous lesions (22 versus LL: OR, 2.27; 95% CI, 1.40-3.70; I(2) = 26.4%; 12 studies). No such association was found for the IL1B-511 (TT versus CC: OR, 1.34; 95% CI, 0.87-2.07; I(2) = 65.7%; 13 studies) or TNFA-308 genotypes (AA versus GG: OR, 0.93; 95% CI, 0.35-2.43; I(2) = 0.0%; 7 studies). The IL1RN22 genotype seems to consistently increase the risk of gastric precancerous lesions, supporting a role for this polymorphism in the early stages of gastric carcinogenesis.
白细胞介素 1（IL1）和肿瘤坏死因子 alpha（TNFA）基因簇内的多态性与胃癌风险增加相关。然而，它们在胃癌前病变中的作用仍知之甚少。我们的目的是对研究白细胞介素 1B-511、白细胞介素 1 受体拮抗剂可变数串联重复和肿瘤坏死因子 alpha-308 基因多态性与胃癌前病变之间关联的进行荟萃分析，包括来自葡萄牙和莫桑比克的原始数据。通过系统评价确定了这些细胞因子基因多态性与胃癌前病变之间关联的已发表研究，并使用随机效应荟萃分析结合了新数据，这些新数据来自接受相同方案内镜和病理评估的葡萄牙志愿船厂工人（n = 215）和莫桑比克消化不良患者（n = 96）。葡萄牙样本中，肠上皮化生的优势比（OR）估计值分别为白细胞介素 1 受体拮抗剂22 基因型 2.83（95%置信区间（95%CI），1.15-6.96）、白细胞介素 1B-511 T 携带者 1.86（95%CI，1.03-3.36）和肿瘤坏死因子 alpha-308AA 基因型 0.59（95%CI，0.12-3.04）。所有患有肠上皮化生的莫桑比克患者均为白细胞介素 1B-511 的 T 携带者，且无白细胞介素 1 受体拮抗剂 2 等位基因。荟萃分析显示，白细胞介素 1 受体拮抗剂22 基因型与胃癌前病变风险增加相关（22 与 LL：OR，2.27；95%CI，1.40-3.70；I（2）=26.4%；12 项研究）。未发现白细胞介素 1B-511（TT 与 CC：OR，1.34；95%CI，0.87-2.07；I（2）=65.7%；13 项研究）或肿瘤坏死因子 alpha-308 基因型（AA 与 GG：OR，0.93；95%CI，0.35-2.43；I（2）=0.0%；7 项研究）存在这种关联。白细胞介素 1 受体拮抗剂22 基因型似乎一致增加胃癌前病变的风险，支持该多态性在胃癌发生的早期阶段的作用。
