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      Investigation of BTLA tagging variants with risk of esophagogastric junction adenocarcinoma

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          Abstract

          Background: Variants in B- and T-lymphocyte attenuator ( BTLA) gene are likely to affect the function of BTLA protein.

          Methods: In the present case–control study, we selected BTLA tagging single-nucleotide polymorphisms (SNPs) (rs16859629 T>C, rs1982809 G>A, rs2171513 G>A and rs3112270 A>G) and conducted a case–control study to identify the association of BTLA SNPs with risk of esophagogastric junction adenocarcinoma (EGJA). The present study involved 1236 new incident EGJA cases and 1540 cancer-free controls.

          Results: The genotypes of BTLA SNPs were analyzed using a SNPscan Kit. No association was also found between the BTLA SNPs and the susceptibility of EGJA in overall comparsion. In subgroup analyses, the BTLA rs1982809 was found to be associated with an increased susceptibility of EGJA (AA versus GG: OR adjusted = 2.09, 95% CI 1.08–4.07, P = 0.030; and AA versus GA/GG: OR adjusted = 1.99, 95% CI 1.04–3.82, P = 0.039). In haplotype comparison, we identified that TAAG haplotype with the order of BTLA rs16859629, rs1982809, rs2171513 and rs3112270 SNPs might increase the susceptibility of EGJA (OR = 3.07, 95% CI = 1.41–6.71; P = 0.003).

          Conclusion: To conclude, the present study suggests that BTLA T rs16859629A rs1982809A rs2171513G rs3112270 haplotype may increase the susceptibility of EGJA. More studies should be conducted to evaluate whether BTLA polymorphisms may influence the susceptibility of cancer in the future.

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          Classification of adenocarcinoma of the oesophagogastric junction.

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            BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.

            During activation, T cells express receptors for receiving positive and negative costimulatory signals. Here we identify the B and T lymphocyte attenuator (BTLA), an immunoglobulin domain-containing glycoprotein with two immunoreceptor tyrosine-based inhibitory motifs. BTLA is not expressed by naive T cells, but it is induced during activation and remains expressed on T helper type 1 (T(H)1) but not T(H)2 cells. Crosslinking BTLA with antigen receptors induces its tyrosine phosphorylation and association with the Src homology domain 2 (SH2)-containing protein tyrosine phosphatases SHP-1 and SHP-2, and attenuates production of interleukin 2 (IL-2). BTLA-deficient T cells show increased proliferation, and BTLA-deficient mice have increased specific antibody responses and enhanced sensitivity to experimental autoimmune encephalomyelitis. B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1).
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              Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.

              Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome-wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer-free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false-positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00-1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67-5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03-1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04-1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever-smokers, non-gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two-factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations. © 2013 Wiley Periodicals, Inc.
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                Author and article information

                Contributors
                Journal
                Biosci Rep
                Biosci. Rep
                bsr
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                20 December 2019
                13 December 2019
                : 39
                : 12
                : BSR20191770
                Affiliations
                [1 ]Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
                [2 ]Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
                [3 ]Department of Medical Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, Fujian Province, China
                Author notes
                Correspondence: Weifeng Tang ( twf001001@ 123456126.com ) or Shuchen Chen ( cscdoctor@ 123456163.com )
                [*]

                These authors have contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-4157-4057
                http://orcid.org/0000-0002-3316-9908
                Article
                BSR20191770
                10.1042/BSR20191770
                6911151
                31774112
                81dfdb47-bea5-4746-9218-70496c33bbdc
                © 2019 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 29 May 2019
                : 08 November 2019
                : 18 November 2019
                : 27 November 2019
                Page count
                Pages: 8
                Categories
                DNA, Chromosomes & Chromosomal Structure
                Genomics
                Immunology & Inflammation
                Molecular Bases of Health & Disease
                Mutation
                Research Articles

                Life sciences
                btla,adenocarcinoma,immune,lymphocyte,polymorphism
                Life sciences
                btla, adenocarcinoma, immune, lymphocyte, polymorphism

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