RESUMO
INTRODUCTION: Gastric cancer (GC) remains a global health challenge, and H. pylori infection is a main risk factor for noncardia GC. The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in mammalian sterile 20-like kinase 1 (MST1) and MST2, H. pylori (H. pylori) infection, and the risk of noncardia gastric cancer (GC). METHODS: A case-control study was conducted using enzyme-linked immunosorbent assay (ELISA) and TaqMan method to detect the titer of anti-H. pylori antibody in normal human serum and genotype 9 SNPs of MST1 and MST2 genes among 808 samples. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and H. pylori infection, as well as the risk of noncardia gastric cancer in codominant, dominant, overdominant, recessive, and log-additive genetic models. Haplotypes were constructed using the Haploview 4.2 software. RESULTS: The CC genotype of MST2 SNP rs10955176 was associated with a reduced risk of H. pylori infection compared to the TT + CT genotype. None of other SNPs were associated with H. pylori infection. The TT genotype of MST2 SNP rs7827435 was associated with a reduced risk of noncardia gastric cancer compared to the AA + AT genotype. None of the SNPs were associated with noncardia gastric cancer. There were no associations between haplotypes and H. pylori infection or the risk of noncardia gastric cancer. CONCLUSIONS: The CC genotype of rs10955176 and the TT genotype of rs7827435 may serve as protective factors against H. pylori infection and noncardia gastric cancer risk, respectively.
Assuntos
Predisposição Genética para Doença , Infecções por Helicobacter , Helicobacter pylori , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas , Humanos , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/complicações , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Feminino , Proteínas Serina-Treonina Quinases/genética , Fator de Crescimento de Hepatócito/genética , Proteínas Proto-Oncogênicas/genética , Idoso , Genótipo , Serina-Treonina Quinase 3 , Fatores de Risco , Adulto , Carcinogênese/genética , Quinases Proteína-Quinases Ativadas por AMP , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
IMPORTANCE: Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.
Assuntos
Coinfecção , Proteínas de Ligação a DNA , Hepacivirus , Vírus da Hepatite B , Hepatite B , Hepatite C , Imunidade Inata , Humanos , Coinfecção/imunologia , Coinfecção/virologia , Proteínas de Ligação a DNA/metabolismo , Hepacivirus/imunologia , Hepatite B/complicações , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Hepatite C/complicações , Hepatite C/imunologia , Hepatite C/virologia , Inflamassomos/metabolismo , Interferon gama/imunologiaRESUMO
BACKGROUND: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori (H. pylori) infection as well as the risk of non-cardia GC. METHODS: First, H. pylori infection was determined by the serological test using enzyme-linked immunoassay. Then genotyping of SNPs was performed for 808 samples by the Taqman method. Finally, unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age and gender, for the association of each SNP with the infection of H. pylori, the risk of non-cardia gastric cancer, as well as the expression of LATS1 and LATS2 proteins in non-cardia GC tissues, using the codominant, dominant, recessive, overdominant, and log-additive inheritance models, respectively. RESULTS: The statistical results showed that LATS2 rs9552315 was associated with H. pylori infection, and the CC + CT genotype could reduce the risk of H. pylori infection (odds ratio [OR]: 0.549, 95% confidence interval [CI]: 0.339-0.881, P < 0.05) compared with the TT genotype in a dominant model. LATS1 rs9393175 was associated with the risk of non-cardia GC, and the AG genotype reduced the risk of non-cardia GC (OR: 0.702, 95% CI: 0.516-0.952, P < 0.05) compared with the GG + AA genotype in an overdominant model. LATS2 rs9509492 was associated with the risk of GC in an log-additive model. No associations were found between five SNPs and expression of LATS1 and LATS2 proteins in non-cardia GC tissue. CONCLUSIONS: LATS2 rs9552315 CT genotype may be a protective factor against infection of H. pylori. LATS1 rs9393175 AG genotype and LATS2 rs9509492 GG genotype may be protective factors for non-cardia GC.