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Polymorphisms in IL-10 and TGF-? gene promoter are associated with lower risk to gastric cancer in a Mexican population.

ABSTRACT: BACKGROUND:Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC. METHODS:The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) patients and 125 asymptomatic controls. DNA was extracted from white blood cells and nine SNPs in cytokine gene promoters were genotyped using predesigned 5'-endonulease assays. The association of the SNPs with IM and GC was evaluated using multinomial regression models. RESULTS:Both genotypes, TC (OR =?0.51, 95% CI?=?0.27-0.98) and TT (OR =?0.42, 95% CI?=?0.20-0.91) in the locus -?509 of the TGF-? promoter were significantly associated with GC. The TT genotype in the locus -?819 of the IL-10 promoter was also significantly associated with GC (OR = 0.37, 95% CI?=?0.17-0.81). No significant association was found with SNPs IL-4 -590?T/C (rs1800629), IL-6 -573G/C (rs1800796), IL-10 -592C/A (rs1800872), IL-10 -1082A/G (rs1800896), and, IFN-? -1615C/T (rs2069705). CONCLUSIONS:SNPs in TGF? (-?509 C/T, rs1800469) and IL-10 (-?819 C/T, rs1800871) promoters were associated with a lower risk for GC in a Mexican population.

SUBMITTER: Martinez-Campos C

PROVIDER: S-EPMC6518715 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Polymorphisms in IL-10 and TGF-β gene promoter are associated with lower risk to gastric cancer in a Mexican population.

Martínez-Campos Cecilia C Torres-Poveda Kirvis K Camorlinga-Ponce Margarita M Flores-Luna Lourdes L Maldonado-Bernal Carmen C Madrid-Marina Vicente V Torres Javier J

BMC cancer 20190515 1

<h4>Background</h4>Helicobacter pylori infection is recognized as the main risk factor for gastric cancer (GC), the fifth most common neoplasia worldwide. H. pylori interacts with the immune system, disrupting the cytokine network and inducing chronic inflammation. This work aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in selected cytokine gene promoters and GC.<h4>Methods</h4>The study included 359 subjects, 125 GC patients, 109 intestinal metaplasia (IM) pat ...[more]

PMID: 31092242

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Project description:Plasmodium falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical host genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity and improve vaccine development initiatives.The effect of single nucleotide polymorphisms (SNPs) and plasma transforming growth factor beta (TGF-?) and interleukin 10 (IL-10) levels on malaria pathology was investigated in a case-control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Thirty-four malaria candidate polymorphisms, including the sickle cell trait (HbS), were assayed on the Sequenom iPLEX platform while plasma TGF-? and IL-10 levels were measured by sandwich ELISA.The study confirms the known protective effect of HbS against severe malaria and also reveals a protective effect of SNPs in the nitrogen oxide synthase 2 (NOS2) gene against malaria infection, anaemia and uncomplicated malaria. Furthermore, ADCY9 rs10775349 (additive G) and ABO rs8176746 AC individuals were associated with protection from hyperpyrexia and hyperparasitaemia, respectively. Meanwhile, individuals with the EMR1 rs373533 GT, EMR1 rs461645 CT and RTN3 rs542998 (additive C) genotypes were more susceptible to hyperpyrexia while both females and males with the rs1050828 and rs1050829 SNPs of G6PD, respectively, were more vulnerable to anaemia. Plasma TGF-? levels were strongly correlated with heterozygosity for the ADCY9 rs2230739 and HBB rs334 SNPs while individuals with the ABO rs8176746 AC genotype had lower IL-10 levels.Taken together, this study suggests that some rare polymorphisms in candidate genes may have important implications for the susceptibility of Cameroonians to severe malaria. Moreover using the uncomplicated malaria phenotype may permit the identification of novel pathways in the early development of the disease.

Dataset Information

Polymorphisms in IL-10 and TGF-? gene promoter are associated with lower risk to gastric cancer in a Mexican population.

Publications

Polymorphisms in IL-10 and TGF-β gene promoter are associated with lower risk to gastric cancer in a Mexican population.

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