Abstract
BackgroundNuclear factor of kappa B inhibitor alpha (IκBα) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of IκBα to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients.MethodsA population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in IκBα were analyzed by TaqMan SNP genotyping assay.ResultsBoth rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients.ConclusionsIκBα rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.
Highlights
Nuclear factor of kappa B inhibitor alpha (IBa) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis
IBa polymorphism was associated with reduced risk of gastric cancer Before genotyping, we conducted Hardy-Weinberg equilibrium analysis of rs2233408 polymorphism
We found that the alleles of rs2233408 polymorphism were in Hardy-Weinberg equilibrium with non-significant c2 values (P = 0.25)
Summary
Nuclear factor of kappa B inhibitor alpha (IBa) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of IBa to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. Polymorphisms in the promoter and exon region in the IBa gene have been reported to be associated with inflammatory diseases and cancers [3,4,5,6,7,8]. We sequenced the 2 kb promoter region of IBa on 32 gastric cancer tissues and 34 normal gastric tissues and found that rs2233408 polymorphism showed bigger difference of the distribution between gastric cancer patients as compared with the control subjects. We conducted a large-scale casecontrol study on Chinese population to investigate the association of rs2233408 polymorphism with gastric cancer or clinicopathologic variables of gastric cancer patients
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