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

Toll-like receptor-2 ( ) is responsible for recognizing ( ) and activating the immune response. Polymorphisms in may modulate gastric carcinogenesis. To evaluate whether the (rs3804099) and - (rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determi...

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Published in:	World journal of gastrointestinal oncology Vol. 12; no. 5; pp. 535 - 548
Main Authors:	Lourenço, Caroline de Matos, Susi, Manoela Dias, do Nascimento, Mariah Cristina Antunes, Serafim Junior, Vilson, Vila, Ana Paula Simedan, Rodrigues-Flemming, Gabriela Helena, Goloni-Bertollo, Eny Maria, Silva, Ana Elizabete, de Oliveira-Cucolo, Juliana Garcia
Format:	Journal Article
Language:	English
Published:	China Baishideng Publishing Group Inc 15-05-2020
Subjects:	Case Control Study Chronic gastritis Helicobacter pylori Gene expression Polymorphisms Toll-like receptor 2 Gastric cancer
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Summary:	Toll-like receptor-2 ( ) is responsible for recognizing ( ) and activating the immune response. Polymorphisms in may modulate gastric carcinogenesis. To evaluate whether the (rs3804099) and - (rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and infection on mRNA expression. 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 Man assay was used to quantify mRNA levels in fresh gastric tissues (48 GC, 36 CG, and 14 C). Regarding the TLR2 -196 to -174 polymorphism, the and 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; < 0.0001). Similarly, an increased risk was observed when comparing the GC and CG groups [codominant ( < 0.0001), dominant ( < 0.0001), recessive ( = 0.0260), overdominant ( < 0.0001) and log-additive ( < 0.0001)]. In contrast, was associated with a protective effect in the GC group compared to the C group [dominant ( = 0.0420) and log-additive ( = 0.0300)]. Regarding the association of polymorphisms with infection, individuals infected with and harboring the TLR2 -196 to -174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant ( = 0.0120), dominant ( = 0.0051), overdominant ( = 0.0240) and log-additive ( = 0.0030)], while was associated with a protective effect [codominant ( = 0.0039), dominant ( < 0.0001), overdominant ( = 0.0097) and log-additive ( = 0.0021)]. mRNA levels were significantly increased in the GC group (median RQ = 6.95) compared to the CG group (RQ = 0.84, < 0.0001) and to the normal mucosa group (RQ = 1.0). In addition, both infection ( < 0.0001) and the presence of the polymorphic del ( = 0.0010) and ( = 0.0004) alleles influenced mRNA expression. The -196 to -174 and polymorphisms are strongly associated with GC. mRNA expression levels are upregulated in neoplastic tissues and influenced by both the presence of and variant genotypes.
Bibliography:	Corresponding author: Ana Elizabete Silva, PhD, Adjunct Professor, Department of Biology, São Paulo State University, Rua Cristóvão Colombo, 2265, São José do Rio Preto, São Paulo 15054-000, Brazil. ae.silva@unesp.br Author contributions: Oliveira-Cucolo JG and Silva AE conceived and designed the experiments; Lourenço CM, Susi MD, Serafim Junior V and Vila APS performed the experiments; Nascimento MCA provided technical support; Oliveira-Cucolo JG, Serafim Junior V and Rodrigues-Flemming GH analyzed and interpreted the data; Silva AE and Goloni-Bertollo EM contributed to the collection of samples/reagents/materials and analysis tools; Oliveira-Cucolo JG, Rodrigues-Flemming, Goloni-Bertollo EM and Silva AE drafted and revised the manuscript; All of the authors approved the final version of the manuscript for publication. Supported by the São Paulo Research Foundation, No. 2013/14022-6 and No. 2014/17716-1.
ISSN:	1948-5204 1948-5204
DOI:	10.4251/wjgo.v12.i5.535