Characterization and strong risk association of TLR2 del -196 to -174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer.

Autor:	Lourenço CM; Department of Graduate-Level Research, Sacred Heart University, Bauru, São Paulo 17011-970, Brazil., Susi MD; Department of Graduate-Level Research, Sacred Heart University, Bauru, São Paulo 17011-970, Brazil., do Nascimento MCA; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil., Serafim Junior V; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil., Vila APS; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil., Rodrigues-Flemming GH; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil., Goloni-Bertollo EM; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil., Silva AE; Department of Biology, São Paulo State University, São José do Rio Preto, São Paulo 15054-000, Brazil. ae.silva@unesp.br., de Oliveira-Cucolo JG; Department of Molecular Biology, São José do Rio Preto School of Medicine, São José do Rio Preto, São Paulo 15090-000, Brazil.
Jazyk:	angličtina
Zdroj:	World journal of gastrointestinal oncology [World J Gastrointest Oncol] 2020 May 15; Vol. 12 (5), pp. 535-548.
DOI:	10.4251/wjgo.v12.i5.535
Abstrakt:	Background: Toll-like receptor-2 ( TLR2 ) is responsible for recognizing Helicobacter pylori ( H. pylori ) and activating the immune response. Polymorphisms in TLR2 may modulate gastric carcinogenesis. Aim: To evaluate whether the TLR2 19216T/C (rs3804099) and TLR2 - 196 to -174 ins/del (rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA expression. Methods: DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples [202 gastric cancer (GC), 269 chronic gastritis (CG), and 383 control/healthy (C)] and genotyped by allele-specific PCR or restriction fragment length polymorphism (RFLP)-PCR. Quantitative polymerase chain reaction by Taq Man ® assay was used to quantify TLR2 mRNA levels in fresh gastric tissues (48 GC, 36 CG, and 14 C). Results: Regarding the TLR2 -196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models (codominant, dominant, recessive, overdominant and log-additive; P < 0.0001). Similarly, an increased risk was observed when comparing the GC and CG groups [codominant ( P < 0.0001), dominant ( P < 0.0001), recessive ( P = 0.0260), overdominant ( P < 0.0001) and log-additive ( P < 0.0001)]. In contrast, TLR2 19216T/C was associated with a protective effect in the GC group compared to the C group [dominant ( P = 0.0420) and log-additive ( P = 0.0300)]. Regarding the association of polymorphisms with H. pylori infection, individuals infected with H. pylori and harboring the TLR2 -196 to -174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant ( P = 0.0120), dominant ( P = 0.0051), overdominant ( P = 0.0240) and log-additive ( P = 0.0030)], while TLR2 19216T/C was associated with a protective effect [codominant ( P = 0.0039), dominant ( P < 0.0001), overdominant ( P = 0.0097) and log-additive ( P = 0.0021)]. TLR2 mRNA levels were significantly increased in the GC group (median RQ = 6.95) compared to the CG group (RQ = 0.84, P < 0.0001) and to the normal mucosa group (RQ = 1.0). In addition, both H. pylori infection ( P < 0.0001) and the presence of the polymorphic TLR2 -196 to -174 del ( P = 0.0010) and TLR2 19216 C ( P = 0.0004) alleles influenced TLR2 mRNA expression. Conclusion: The TLR2 -196 to -174 ins/del and TLR2 19216 T/C polymorphisms are strongly associated with GC. TLR2 mRNA expression levels are upregulated in neoplastic tissues and influenced by both the presence of H. pylori and variant genotypes. Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare. (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
Databáze:	MEDLINE
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