Interleukin-4 and -8 Gene Polymorphisms and Risk of Gastric Cancer in a Population in Southwestern China


Background: Gastric carcinogenesis is a complicated process that involves environmental and genetic factorslike interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changedlevels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A andgastric cancer (GC) risk in Sichuan of Southwestern China. Materials and
Methods: We surveyed the researchsubjects using a self-designed questionnaire with questions on demographic factors and putative risk factors.Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>Agenotypes using MALDI-TOF MS.
Results: Our study recruited 308 pairs of GC patients and controls, including224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients inthe case group. The case and control groups had an average age of 57.7±10.6 (mean±SD) and 57.6±11.1 years.GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01)and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>Awere not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjustedOR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites onlyfound that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjustedOR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking(adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardiaGC.
Conclusions: Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overallGC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to theevidence body for risk of SNPs associated with the development of gastric cancer in this region.