Human Genetics Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Santiago, Chile
Department of Gastroenterology, University of Chile Clinical Hospital, Santiago, Chile Department of Surgery, University of Chile Clinical Hospital, Santiago, Chile.
Anticancer Res. 2014 Jul;34(7):3523-30.
To assess the role of pro- and anti-inflammatory polymorphisms in gastric cancer susceptibility.
We genotyped 12 polymorphisms in eight cytokine genes (Interleukin-1β -IL1B-, IL8, IL17A, IL17F, IL32, tumor necrosis factor-α -TNF-, IL1RN, IL10) in a case-control study of 147 patients with gastric cancer and 172 controls.
Single polymorphism analysis revealed an association between the IL10 -592C>A single nucleotide polymorphism and cases with moderately- or well-differentiated tumors [AA vs. GG, odds ratio (OR)=3.01; 95% confidence interval (CI)=1.08-8.50]. We further analyzed gene-gene interactions using a combined attribute network implemented in multifactor dimensionality reduction software. The analysis revealed an interaction between IL8 -251A>T and IL32 rs28372698 SNPs among cases with moderately- or well-differentiated tumors. Homozygosity for both IL8 -251T and IL32 T alleles increases the odds for developing gastric cancer up to 2.63-fold (OR=2.63; 95% CI=1.15-6.03). This association was higher compared to the homozygosity for the IL8-251 T allele alone (OR=1.11; 95% CI=0.51-2.43) or the IL32 T allele alone (OR=1.21; 95% CI=0.54-2.72).
These findings suggest that IL10 -592C>A increases the odds for developing gastric cancer. An interaction between IL8 -251A>T and IL32 rs28372698 SNPs is also proposed.
评估前炎症和抗炎基因多态性在胃癌易感性中的作用。
我们在 147 例胃癌患者和 172 例对照的病例对照研究中,对 8 个细胞因子基因(白细胞介素 1β-IL1B-、IL8、IL17A、IL17F、IL32、肿瘤坏死因子-α-TNF-、IL1RN、IL10)中的 12 个多态性进行了基因分型。
单核苷酸多态性分析显示,IL10-592C>A 单核苷酸多态性与中-高分化肿瘤病例之间存在相关性[AA 与 GG,比值比(OR)=3.01;95%置信区间(CI)=1.08-8.50]。我们进一步使用多因子维度降低软件中的组合属性网络分析了基因-基因相互作用。分析显示,中-高分化肿瘤病例中 IL8-251A>T 和 IL32 rs28372698 SNP 之间存在相互作用。IL8-251T 和 IL32 T 等位基因的纯合性使胃癌发病风险增加高达 2.63 倍(OR=2.63;95%CI=1.15-6.03)。与 IL8-251T 等位基因纯合性(OR=1.11;95%CI=0.51-2.43)或 IL32 T 等位基因纯合性(OR=1.21;95%CI=0.54-2.72)相比,这种相关性更高。
这些发现表明,IL10-592C>A 增加了患胃癌的几率。还提出了 IL8-251A>T 和 IL32 rs28372698 SNP 之间的相互作用。