IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-β pro-inflammatory cytokine is not

Abstract

Genetic polymorphisms in genes that codify inflammatory cytokines have been associated with gastric carcinogenesis. This study evaluated polymorphisms IL-1RN VNTR and TNFB+252A/G in a population from Southeast Brazil with regard to the risk of chronic gastritis and gastric cancer and the presence of an association of gastric lesions with risk factors such as gender, age, smoking, drinking and Helicobacter pylori infection. In this case-control study, polymorphism at IL-1RN VNTR was investigated using the allele-specific polymerase chain reaction method, while the polymerase chain reaction-restriction fragment length polymorphism technique was used to identify the TNFB+252A/G genotype in 675 Brazilian individuals [229 with chronic gastritis (CG), 200 with gastric cancer (GC) and 246 healthy individuals as controls (C)]. Multiple logistic regression analysis (log-additive, dominant, and recessive models) have not showed association of the genotype frequencies for the SNP TNFB + 252A/G with risk of CG or GC. However, as for IL-1RN VNTR it was observed significant differences in all three analysis models, with higher values of OR in recessive model, both in the GC group (OR = 3.04, 95% CI = 1.41-6.56, p < 0.01) and CG (OR = 2.32, 95% CI = 1.10-4.90, p = 0.02) compared to the C group. In addition, the multiple logistic regression showed also an association with risk factors such as male gender, older age and alcohol intake regarded GC group. So, our results indicated that the IL-1RN*2 allele may increase the risk of gastric cancer and precancerous lesions in the Southeast Brazilian population, reinforcing the importance of host genetic factors in the susceptibility to gastric cancer and the participation of cytokines in both the inflammation and the carcinogenic process.

Gene-diet interactions in gastric cancer risk: A systematic review

“…Boccia et al [39] reported that the [50] , 2012, Brazil Zhang et al [56] , positive association between gastric cancer risk and high consumption of grilled/barbecued meat in Italy was more pronounced among SULT1A1 His/His carriers compared with Arg/Arg carriers. It is possible that low enzyme activity in the individuals with SULT1A1 His/His genotype may result in less detoxification of HCAs from high consumption of grilled/barbequed meat [39] .…”

“…In those who consume fewer soybeans, IL-10 genetic variants may allow infection with more virulent H. pylori strains and increase gastric inflammation [49] . Oliveira et al [50] investigated the modifying effects of alcohol on the association between genetic polymorphisms anti-or pro-inflammatory cytokines and gastric cancer risk in Southeast Brazilians but found no significant interactions.…”

Association of single nucleotide polymorphisms in pro-inflammatory cytokine and toll-like receptor genes with pediatric hematogenous osteomyelitis

“…They are located within the coding and promoter regions of genes, and thereby affect gene function. Several SNPs are associated with susceptibility to infectious disease (Lu et al, 2005;Reale et al, 2011;Oliveira et al, 2012;Christaki and Giamarellos-Bourboulis, 2014). Although their functional role remains to be established, several SNPs are believed to affect the production of cytokines (Tsezou et al, 2008).…”

Influence of functional polymorphisms in TNF-α, IL-8, and IL-10 cytokine genes on mRNA expression levels and risk of gastric cancer

“…The first step was a case-control study on chronic gastritis (CG) and gastric cancer (GC), in which a total of 723 peripheral blood DNA samples from a previous study [26], which had been stored in our laboratory and genotyped for cytokine polymorphisms, were assessed. The first case group comprised 276 patients (142 men and 134 women) with a histopathologically confirmed diagnosis of chronic gastritis according to the Sidney System [27] and a mean age of 53.7±14.41 years (range 19-86 years).…”