Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal squamous cell carcinoma in the Kazakh population but is not associated with HPV infection
The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study,...
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| Published in | PloS one Vol. 12; no. 10; p. e0186319 |
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| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Public Library of Science
26.10.2017
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| Abstract | The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. |
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| AbstractList | The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC.The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83×10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076–2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168–3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286–0.621, p = 8.83×10 −6 ). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth ( p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076–2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168–3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286–0.621, p = 8.83×10−6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. The Kazakh population in Xinjiang Province in northwestern China exhibits a high incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of esophageal carcinoma (EC) has not been elucidated, there are reports of the involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC patients and 500 age- and sex-matched control subjects were recruited. DNA was extracted from paraffin-embedded tumor specimens from the patients and peripheral blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We found a clear increased risk of ESCC in the Kazakh population for the heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011 for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p = 8.83x10.sup.-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild-type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased susceptibility to ESCC. This is the first study to report that the heterozygous LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the Kazakh population and that the heterozygous LMP7 Q/K genotype decreases susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7 was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7 genetic variability will provide a new therapeutic perspective for Kazakh patients with ESCC. |
| Audience | Academic |
| Author | Li, Mei Hu, Jianming Pang, Lijuan Cui, Xiaobin Wu, Fei Li, Feng Yang, Lan Chen, Yunzhao Wei, Yutao Ji, Yu Chen, Ling Jiang, Jinfang |
| AuthorAffiliation | 1 Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China Fondazione IRCCS Istituto Nazionale dei Tumori, ITALY 2 The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China 3 Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China |
| AuthorAffiliation_xml | – name: 2 The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China – name: 3 Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China – name: Fondazione IRCCS Istituto Nazionale dei Tumori, ITALY – name: 1 Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China |
| Author_xml | – sequence: 1 givenname: Lan orcidid: 0000-0002-8880-9466 surname: Yang fullname: Yang, Lan – sequence: 2 givenname: Yu surname: Ji fullname: Ji, Yu – sequence: 3 givenname: Ling surname: Chen fullname: Chen, Ling – sequence: 4 givenname: Mei surname: Li fullname: Li, Mei – sequence: 5 givenname: Fei surname: Wu fullname: Wu, Fei – sequence: 6 givenname: Jianming surname: Hu fullname: Hu, Jianming – sequence: 7 givenname: Jinfang surname: Jiang fullname: Jiang, Jinfang – sequence: 8 givenname: Xiaobin surname: Cui fullname: Cui, Xiaobin – sequence: 9 givenname: Yunzhao surname: Chen fullname: Chen, Yunzhao – sequence: 10 givenname: Lijuan surname: Pang fullname: Pang, Lijuan – sequence: 11 givenname: Yutao surname: Wei fullname: Wei, Yutao – sequence: 12 givenname: Feng surname: Li fullname: Li, Feng |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29073155$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3390_cancers15235604 crossref_primary_10_1016_j_cancergen_2019_07_003 crossref_primary_10_3892_ol_2019_9904 crossref_primary_10_1016_j_humimm_2020_07_002 crossref_primary_10_3390_ijms19030868 crossref_primary_10_3892_ol_2019_10900 crossref_primary_10_1021_acs_chemrestox_1c00156 crossref_primary_10_3389_fonc_2021_605106 |
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| Copyright | COPYRIGHT 2017 Public Library of Science 2017 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2017 Yang et al 2017 Yang et al |
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| SubjectTerms | Alphapapillomavirus - pathogenicity Antigens Biology and Life Sciences Cancer therapies Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - virology Case-Control Studies China Complications and side effects Cysteine Endopeptidases - genetics Cytokines Cytotoxicity Deoxyribonucleic acid Development and progression DNA Esophageal cancer Esophageal carcinoma Esophageal Neoplasms - genetics Esophageal Neoplasms - pathology Esophageal Neoplasms - virology Esophageal Squamous Cell Carcinoma Esophagus Ethnic Groups Etiology Female Gene expression Gene polymorphism Genetic aspects Genetic Predisposition to Disease Genetic variability Genotypes Genotyping Haplotypes Health aspects Hospitals Human papillomavirus Humans Infections Laboratories Linkage Disequilibrium LMP7 gene Lymphocytes Male Medical research Medicine Medicine and Health Sciences Middle Aged Mortality Ovarian cancer Papillomavirus infections Paraffin Pathology Patients People and Places Peripheral blood Physiological aspects Polymerase chain reaction Polymorphism Polymorphism, Single Nucleotide Population Proteasome Endopeptidase Complex - genetics Research and Analysis Methods Restriction fragment length polymorphism Risk factors Risk reduction Single nucleotide polymorphisms Single-nucleotide polymorphism Squamous cell carcinoma Studies Variability Viral infections |
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| Title | Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal squamous cell carcinoma in the Kazakh population but is not associated with HPV infection |
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