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Population, Epidemiological, and Functional Genetics of Gastric Cancer Candidate Genes in Peruvians with Predominant Amerindian Ancestry

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dc.contributor.author Zamudio, Roxana
dc.contributor.author Pereira, Latife
dc.contributor.author Rocha, Carolina D.
dc.contributor.author Berg, Douglas E.
dc.contributor.author Muniz-Queiroz, Thais
dc.contributor.author Sant Anna, Hanaisa P.
dc.contributor.author Cabrera, Lilia
dc.contributor.author Combe, Juan M.
dc.contributor.author Herrera, Phabiola
dc.contributor.author Jahuira, Martha H.
dc.contributor.author Leao, Felipe B.
dc.contributor.author Lyon, Fernanda
dc.contributor.author Prado, William A.
dc.contributor.author Rodrigues, Maira R.
dc.contributor.author Rodrigues-Soares, Fernanda
dc.contributor.author Santolalla, Meddly L.
dc.contributor.author Zolini, Camila
dc.contributor.author Silva, Aristobolo M.
dc.contributor.author Gilman, Robert H.
dc.contributor.author Tarazona-Santos, Eduardo
dc.contributor.author Kehdy, Fernanda S. G.
dc.date.accessioned 2019-02-06T14:52:19Z
dc.date.available 2019-02-06T14:52:19Z
dc.date.issued 2015
dc.identifier.uri https://hdl.handle.net/20.500.12866/5303
dc.description.abstract Background. Gastric adenocarcinoma is associated with chronic infection by Helicobacter pylori and with the host inflammatory response triggered by it, with substantial inter-person variation in the immune response profile due to host genetic factors. Aim. To investigate the diversity of the proinflammatory genes IL8, its receptors and PTGS2 in Amerindians; to test whether candidate SNPs in these genes are associated with gastric cancer in an admixed population with high Amerindian ancestry from Lima, Peru; and to assess whether an IL8RB promoter-derived haplotype affects gene expression. Methods. We performed a Sanger-resequencing population survey, a candidate-gene association study (220 cases, 288 controls) and meta-analyses. We also performed an in vitro validation by a reporter gene assay of IL8RB promoter. Results. The diversity of the promoter of studied genes in Native Americans is similar to Europeans. Although an association between candidate SNPs and gastric cancer was not found in Peruvians, trend in our data is consistent with meta-analyses results that suggest PTGS2-rs689466-A is associated with H. pylori-associated gastric cancer in East Asia. IL8RB promoter-derived haplotype (rs3890158-A/rs4674258-T), common in Peruvians, was up-regulated by TNF-α unlike the ancestral haplotype (rs3890158-G/rs4674258-C). Bioinformatics analysis suggests that this effect stemmed from creation of a binding site for the FOXO3 transcription factor by rs3890158G>A. Conclusions. Our updated meta-analysis reinforces the role of PTGS2-rs689466-A in gastric cancer in Asians, although more studies that control for ancestry are necessary to clarify its role in Latin Americans. Finally, we suggest that IL8RB-rs3890158G>A is a cis-regulatory SNP. en_US
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof urn:issn:1573-2568
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Humans en_US
dc.subject Peru/epidemiology en_US
dc.subject Case-Control Studies en_US
dc.subject Risk Factors en_US
dc.subject Phenotype en_US
dc.subject Computational Biology en_US
dc.subject African Continental Ancestry Group/genetics en_US
dc.subject European Continental Ancestry Group/genetics en_US
dc.subject Ancestry en_US
dc.subject Amerindians en_US
dc.subject Polymorphism, Single Nucleotide en_US
dc.subject Genetic Predisposition to Disease en_US
dc.subject Adenocarcinoma/ethnology/genetics/metabolism en_US
dc.subject Asian Continental Ancestry Group/genetics en_US
dc.subject Association studies en_US
dc.subject Binding Sites en_US
dc.subject Biomarkers, Tumor/genetics en_US
dc.subject Cyclooxygenase 2/genetics en_US
dc.subject Forkhead Box Protein O3 en_US
dc.subject Forkhead Transcription Factors/genetics/metabolism en_US
dc.subject Gastric cancer en_US
dc.subject Gene Expression Regulation, Neoplastic en_US
dc.subject Gene Frequency en_US
dc.subject Genetic Association Studies en_US
dc.subject Haplotypes en_US
dc.subject HEK293 Cells en_US
dc.subject Indians, South American/genetics en_US
dc.subject Interleukin-8/genetics en_US
dc.subject Meta-analyses en_US
dc.subject Proinflammatory genes en_US
dc.subject Promoter Regions, Genetic en_US
dc.subject Stomach Neoplasms/ethnology/genetics/metabolism en_US
dc.subject Transfection en_US
dc.title Population, Epidemiological, and Functional Genetics of Gastric Cancer Candidate Genes in Peruvians with Predominant Amerindian Ancestry en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1007/s10620-015-3859-6
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.19

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