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Xie Y, Yu Y, Wu H, Gao H, Yang Z, Zhang Y, Zhang X. XAB2 TagSNP Is Associated with the Risk of Gastric Cancer in Chinese Population: A Case-Control Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18041494. [PMID: 33557438 PMCID: PMC7914850 DOI: 10.3390/ijerph18041494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/31/2021] [Accepted: 02/02/2021] [Indexed: 11/26/2022]
Abstract
XAB2 protein (xeroderma pigmentosum group A-binding protein 2) plays a significant role in the nucleotide excision repair pathway. Polymorphisms in the XAB2 gene may have an effect on the capability of DNA repair and further contribute to the risk of developing various cancers. In order to investigate the relationship between XAB2 genetic variants and the risk of gastric cancer, we performed a hospital-based case–control study. XAB2 tagSNPs were selected and then genotyped by iPlex Gold Genotyping Assay and Sequenom MassArray. By performing logistic regression analysis, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association of XAB2 tagSNPs with the risk of gastric cancer. Our results showed that XAB2 rs794078AA genotype was associated with a significantly lower risk of gastric cancer compared with GG genotype with OR (95% CI) of 0.33 (0.12–0.91). Stratified analysis indicated a significantly decreased risk for gastric cancer among smokers with rs794078AA genotype compared with nonsmokers with GG genotype (OR = 0.11, 95% CI = 0.01–0.91, p = 0.040). The gene–gene interactions by multifactor dimensionality reduction (MDR) showed that tagSNP rs794078 was the best predictive element for gastric cancers (Testing Bal. Acc = 51.68%, p = 0.055, cross-validation consistency = 9). Therefore, the XAB2 tagSNP rs794078 may play an important role in the development of gastric cancer.
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Affiliation(s)
- Yuning Xie
- School of Public Health, North China University of Science and Technology, Tangshan 063210, China; (Y.X.); (H.W.); (H.G.)
- College of Life Science, North China University of Science and Technology, Tangshan 063210, China;
| | - Yuan Yu
- College of Life Science, North China University of Science and Technology, Tangshan 063210, China;
| | - Hongjiao Wu
- School of Public Health, North China University of Science and Technology, Tangshan 063210, China; (Y.X.); (H.W.); (H.G.)
| | - Hui Gao
- School of Public Health, North China University of Science and Technology, Tangshan 063210, China; (Y.X.); (H.W.); (H.G.)
| | - Zhenbang Yang
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China; (Z.Y.); (Y.Z.)
| | - Yi Zhang
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan 063210, China; (Z.Y.); (Y.Z.)
| | - Xuemei Zhang
- School of Public Health, North China University of Science and Technology, Tangshan 063210, China; (Y.X.); (H.W.); (H.G.)
- College of Life Science, North China University of Science and Technology, Tangshan 063210, China;
- Correspondence: ; Tel.: +86-3158805603
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Yang ML, Huang Z, Wu LN, Wu R, Ding HX, Wang BG. lncRNA- PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility. Biosci Rep 2019; 39:BSR20190708. [PMID: 31253700 PMCID: PMC6629943 DOI: 10.1042/bsr20190708] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/29/2019] [Accepted: 06/25/2019] [Indexed: 12/18/2022] Open
Abstract
Background: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.
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Affiliation(s)
- Ming-Li Yang
- The 2nd Oncology Department of Affiliated Shengjing Hospital of China Medical University, Shenyang 110022, China
| | - Zhe Huang
- Genery Surgery Department of Affiliated Shengjing Hospital of China Medical University, Shenyang 110015, China
| | - Li-Na Wu
- The 2nd Oncology Department of Affiliated Shengjing Hospital of China Medical University, Shenyang 110022, China
| | - Rong Wu
- The 2nd Oncology Department of Affiliated Shengjing Hospital of China Medical University, Shenyang 110022, China
| | - Han-Xi Ding
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Ben-Gang Wang
- Department 1 of General Surgery, the First Hospital of China Medical University, Shenyang 110001, China
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Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene. BMC MEDICAL GENETICS 2018; 19:182. [PMID: 30290787 PMCID: PMC6173921 DOI: 10.1186/s12881-018-0698-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 09/25/2018] [Indexed: 12/17/2022]
Abstract
Background It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the − 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the −202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly. Methods The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes. Results The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388–0.909), as well as with the female (OR 0.385, 95% CI 0.206–0.72), macroadenoma (OR 0.557, 95% CI 0.347–0.893) and monotherapy (OR 0.512, 95% CI 0.316–0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331). Conclusion This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.
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Wang BG, Xu Q, Lv Z, Fang XX, Ding HX, Wen J, Yuan Y. Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study. World J Gastroenterol 2018; 24:2482-2490. [PMID: 29930469 PMCID: PMC6010940 DOI: 10.3748/wjg.v24.i23.2482] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 04/17/2018] [Accepted: 05/18/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the association of 12 tag single nucleotide polymorphisms (tagSNPs) in three onco-long non-coding RNA (lncRNA) genes (HOTTIP, CCAT2, MALAT1) with the risk and prognosis of hepatocellular cancer (HCC).
METHODS Twelve tagSNPs covering the three onco-lncRNAs were genotyped by the KASP method in a total of 1338 samples, including 521 HCC patients and frequency-matched 817 controls. The samples were obtained from an unrelated Chinese population at the First Hospital of China Medical University from 2012-2015. The expression quantitative trait loci (eQTL) analyses were conducted to explore further the potential function of the promising SNPs.
RESULTS Three SNPs in HOTTIP, one promoter SNP in MALAT1, and one haplotype of HOTTIP were associated with HCC risk. The HOTTIP rs17501292, rs2067087, and rs17427960 SNPs were increased to 1.55-, 1.20-, and 1.18-fold HCC risk under allelic models (P = 0.012, 0.017 and 0.049, respectively). MALAT1 rs4102217 SNP was increased to a 1.32-fold HCC risk under dominant models (P = 0.028). In addition, the two-way interaction of HOTTIP rs17501292-MALAT1 rs619586 polymorphisms showed a decreased effect on HCC risk (Pinteraction = 0.028, OR = 0.30) and epistasis with each other. HOTTIP rs3807598 variant genotype showed significantly longer survival time in HBV negative subgroup (P = 0.049, HR = 0.12), and MALAT1 rs591291 showed significantly better prognosis in female and HBV negative subgroups (P = 0.022, HR = 0.37; P = 0.042, HR = 0.25, respectively). In the study, no significant effect was observed in eQTL analysis.
CONCLUSION Specific lncRNA (HOTTIP and MALAT1) SNPs have potential to be biomarkers for HCC risk and prognosis.
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Affiliation(s)
- Ben-Gang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
- Hepatobiliary Surgery Department of General Surgery Institute, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
| | - Zhi Lv
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
| | - Xin-Xin Fang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
| | - Han-Xi Ding
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
| | - Jing Wen
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, Liaoning Province, China
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The association of lncRNA-HULC polymorphisms with hepatocellular cancer risk and prognosis. Gene 2018; 670:148-154. [PMID: 29803923 DOI: 10.1016/j.gene.2018.05.096] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 05/10/2018] [Accepted: 05/23/2018] [Indexed: 02/09/2023]
Abstract
BACKGROUND Genetic polymorphisms in lncRNA HULC may affect the susceptibility and clinical outcome of cancer. We aimed to investigate the association of HULC tagSNPs with the risk and prognosis of hepatocellular cancer, as well as the influence of the SNPs on lncRNA expression level. METHODS A total of 1338 samples were recruited in the risk study. Among them, 351 HCC patients were involved in the prognosis study. SNP genotyping was performed using KASP method and lncRNA expression was detected by Real-time PCR. RESULTS We found a promoter SNP, rs1041279, was associated with a 1.41-fold increased HCC risk (P = 0.032). In the stratified analysis, rs1041279 had greater ORs for the increased HCC risk in the male subgroup (P = 0.014, OR = 1.54). Furthermore, multi-logistic regression analysis revealed a two-way interaction effect of smoking-rs2038540 SNP on HCC risk (OR = 4.20). And MDR analysis consistently demonstrated a SNP-environmental interaction among smoking-drinking-rs2038540 SNP as the best model for predicting HCC risk (P = 0.0107). In our study, no significant association was found between HULC SNPs and the overall survival (P > 0.05), and no significant effect was observed of rs1041279 SNP on lncRNA-HULC expression (P > 0.05). CONCLUSION lncRNA-HULC rs1041279 SNP and the interaction of rs2038540 SNP with environmental factors could enhance HCC risk.
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Carrera-Lasfuentes P, Lanas A, Bujanda L, Strunk M, Quintero E, Santolaria S, Benito R, Sopeña F, Piazuelo E, Thomson C, Pérez-Aisa A, Nicolás-Pérez D, Hijona E, Espinel J, Campo R, Manzano M, Geijo F, Pellise M, Zaballa M, González-Huix F, Espinós J, Titó L, Barranco L, D'Amato M, García-González MA. Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype. Oncotarget 2018; 8:35848-35862. [PMID: 28415781 PMCID: PMC5482622 DOI: 10.18632/oncotarget.16261] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 02/27/2017] [Indexed: 12/21/2022] Open
Abstract
Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.
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Affiliation(s)
| | - Angel Lanas
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.,Faculty of Medicine, Universidad de Zaragoza, Zaragoza, Spain
| | - Luis Bujanda
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Mark Strunk
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
| | - Enrique Quintero
- Department of Gastroenterology, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB), Centro de Investigación Biomédica de Canarias (CIBICAN), Tenerife, Spain
| | | | - Rafael Benito
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,Faculty of Medicine and Department of Microbiology, Hospital Clínico Universitario, Zaragoza, Spain
| | - Federico Sopeña
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,Department of Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
| | - Elena Piazuelo
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
| | - Concha Thomson
- Department of Gastroenterology, Hospital Obispo Polanco, Teruel, Spain
| | | | - David Nicolás-Pérez
- Department of Gastroenterology, Hospital Universitario de Canarias, Instituto Universitario de Tecnologías Biomédicas (ITB), Centro de Investigación Biomédica de Canarias (CIBICAN), Tenerife, Spain
| | - Elizabeth Hijona
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Department of Gastroenterology, Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Jesús Espinel
- Department of Gastroenterology, Complejo Hospitalario, León, Spain
| | - Rafael Campo
- Department of Gastroenterology, Hospital Parc Tauli, Sabadell, Spain
| | - Marisa Manzano
- Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
| | - Fernando Geijo
- Department of Gastroenterology, Hospital Clínico Universitario, Salamanca, Spain
| | - María Pellise
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Department of Gastroenterology, Hospital Clinic I Provincial, Institut d Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain
| | - Manuel Zaballa
- Department of Gastroenterology, Hospital de Cruces, Barakaldo, Spain
| | | | - Jorge Espinós
- Department of Gastroenterology, Mutua de Tarrasa, Spain
| | - Llúcia Titó
- Department of Gastroenterology, Hospital de Mataró, Mataró, Spain
| | - Luis Barranco
- Department of Gastroenterology, Hospital del Mar, Barcelona, Spain
| | - Mauro D'Amato
- BioDonostia Health Research Institute, IKERBASQUE, Basque Foundation for Science, San Sebastián, Spain
| | - María Asunción García-González
- CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.,Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain
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Wang B, Xu Q, Yang HW, Sun LP, Yuan Y. The association of six polymorphisms of five genes involved in three steps of nucleotide excision repair pathways with hepatocellular cancer risk. Oncotarget 2018; 7:20357-67. [PMID: 26967386 PMCID: PMC4991460 DOI: 10.18632/oncotarget.7952] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 02/15/2016] [Indexed: 12/14/2022] Open
Abstract
Background Hundreds of single nucleotide polymorphisms (SNPs) of the genes encoding nucleotide excision repair (NER) proteins are involved in every step of the DNA recognition–unwinding–incision process, which may affect cancer risk. However, only a limited number of studies have examined the association of NER SNPs with hepatocellular cancer (HCC) risk. Results In screening stage, single-locus analysis showed that six SNPs in five genes were associated with HCC risk, including three risk SNPs (XPA rs10817938, XPC rs1870134 and ERCC2 rs238417) and three protective SNPs (ERCC1 rs2298881 and rs3212961, and ERCC5 rs873601). In verification stage, only XPC rs1870134 was verified to be associated with HCC risk (P = 4.7 × 10−4). Furthermore, multivariate logistic regression and MDR analysis consistently revealed a gene–gene interaction among ERCC1 rs2298881 and XPC rs1870134 SNPs associated with HCC risk (Pinteraction = 0.023). When analyzing the effect of the positive SNP on the mRNA expression, we found XPC rs1870134 GG genotype which was associated with an increased HCC risk showed lower XPC mRNA expression. Methods This study designed as “screening-verification” experiments and included a total of 1472 participants (570 HCC patients vs. 902 controls). We explored 39 SNPs in eight genes involved in NER Pathways, including XPA, XPC, DDB2, ERCC3, ERCC2, ERCC1, ERCC4 and ERCC5, using Sequenom MassARRAY and KASPar platform. Eighty-six cases of HCC and the neighboring noncancerous tissues were subjected to the measurement of mRNA expression level of the promising gene. Conclusions XPC promoter rs1870134 SNP and SNP-SNP interaction were associated with HCC risk.
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Affiliation(s)
- Bengang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.,Hepatobiliary Surgery Department of General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Huai-Wei Yang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Li-Ping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
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Nie Y, Wu K, Yu J, Liang Q, Cai X, Shang Y, Zhou J, Pan K, Sun L, Fang J, Yuan Y, You W, Fan D. A global burden of gastric cancer: the major impact of China. Expert Rev Gastroenterol Hepatol 2017; 11:651-661. [PMID: 28351219 DOI: 10.1080/17474124.2017.1312342] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Gastric cancer (GC) is a highly aggressive cancer and a major cause of cancer-related deaths worldwide. Approximately half of the world's GC cases and deaths occur in china. GC presents challenges in early diagnosis and effective therapy due to a lack of understanding of the underlying molecular biology. The primary goals of this review are to outline current GC research in china and describe future trends in this field. Areas covered: This review mainly focuses on a series of GC-related advances China has achieved. Considerable progress has been made in understanding the role of H. pylori in GC by a series of population-based studies in well-established high-risk areas; A few germline and somatic alterations have been identified by 'omics' studies; Studies on the mechanisms of malignant phenotypes have helped us to form an in-depth understanding of GC and advance drug discovery. Moreover, identification of potential biomarkers and targeted therapies have facilitated the diagnosis and treatment of GC. However, many challenges remain. Expert commentary: To combat GC, sufficient funding is important. More attention should be paid on early diagnosis and the discovery of novel efficient biomarkers and the development of biomarker-based or targeted therapeutics in GC.
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Affiliation(s)
- Yongzhan Nie
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Kaichun Wu
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jun Yu
- b Department of Medicine and Therapeutics and Institute of Digestive Disease , Chinese University of Hong Kong , Hong Kong , China
| | - Qiaoyi Liang
- b Department of Medicine and Therapeutics and Institute of Digestive Disease , Chinese University of Hong Kong , Hong Kong , China
| | - Xiqiang Cai
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Yulong Shang
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Jinfeng Zhou
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
| | - Kaifeng Pan
- c Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology , Peking University Cancer Hospital & Institute , Beijing , China
| | - Liping Sun
- d Tumor Etiology and Screening, Department of Cancer Institute and General Surgery , The First Affiliated Hospital of China Medical University , Shenyang , China
| | - Jingyuan Fang
- e Renji Hospital , Shanghai Jiao-Tong University School of Medicine , Shanghai , China
| | - Yuan Yuan
- d Tumor Etiology and Screening, Department of Cancer Institute and General Surgery , The First Affiliated Hospital of China Medical University , Shenyang , China
| | - Weicheng You
- c Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University School of Oncology , Peking University Cancer Hospital & Institute , Beijing , China
| | - Daiming Fan
- a State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
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Sun P, Du J, Zhu X, Ren C, Xie L, Dai N, Gu Y, Yan C, Dai J, Ma H, Jiang Y, Chen J, Hu Z, Shen H, Wu H, Jin G. Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population. PLoS One 2015; 10:e0139059. [PMID: 26402912 PMCID: PMC4581712 DOI: 10.1371/journal.pone.0139059] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 09/07/2015] [Indexed: 01/28/2023] Open
Abstract
NBN plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the NBN gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the NBN gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in NBN and gastric cancer risk in a case-control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71-0.94; P = 4.71×10-3). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59-0.88], P = 1.07×10-3), and male individuals (per-allele OR = 0.73[0.62-0.87], P = 3.68×10-4). We further conducted a haplotype analysis and identified that the NBN Ars10464867Grs14448Grs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65-0.89], P = 6.39×10-4). In summary, these findings indicate that genetic variants at NBN gene may contribute to gastric cancer susceptibility and may further advance our understanding of NBN gene in cancer development.
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Affiliation(s)
- Ping Sun
- Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- Department of Pathology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214006, China
| | - Jiangbo Du
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Xun Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Chuanli Ren
- Medical Lab, Northern Jiangsu People’s Hospital, Yangzhou 225001, China
| | - Lan Xie
- Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China
| | - Ningbin Dai
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Yayun Gu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Caiwang Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Juncheng Dai
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Hongxia Ma
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Yue Jiang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Jiaping Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Zhibin Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Hongbing Shen
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
| | - Haorong Wu
- Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
- * E-mail: (GJ); (HW)
| | - Guangfu Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China
- * E-mail: (GJ); (HW)
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Lin J, Hu B, Wang M. Lack of association between XPF polymorphisms and gastric cancer risk: a meta-analysis. Oncol Res Treat 2014; 37:546-52. [PMID: 25342505 DOI: 10.1159/000367801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 08/18/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND Xeroderma pigmentosum complementation group F (XPF or ERCC4) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. Several epidemiological studies have examined associations between XPF polymorphisms and gastric cancers risk, but the findings remain inconclusive. Therefore, we conducted the present meta-analysis to obtain the most reliable estimate of the association. METHODS PubMed, Embase, Web of Science, and Wanfang were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between 3 commonly studied polymorphisms of XPF (rs744154, rs6498486, rs1799801) and gastric cancer risk. The pooled ORs were performed for the co-dominant model (homozygous and heterozygous), dominant model, and recessive model. 3 studies on rs744154, 3 studies on rs6498486, and 4 studies on rs1799801 were included in our meta-analysis. RESULTS Our results show that the genotype distribution of the 3 polymorphisms was not associated with risk of gastric cancer in all genetic models. CONCLUSION This meta-analysis suggests that the 3 common XPF polymorphisms rs744154, rs6498486, and rs1799801 are not associated with gastric cancer risk. However, large-sample and representative population-based studies with homogeneous gastric cancer patients and well-matched controls are warranted to confirm this finding.
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Affiliation(s)
- Jiaying Lin
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
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Liu J, He C, Xing C, Yuan Y. Nucleotide excision repair related gene polymorphisms and genetic susceptibility, chemotherapeutic sensitivity and prognosis of gastric cancer. Mutat Res 2014; 765:11-21. [PMID: 24769428 DOI: 10.1016/j.mrfmmm.2014.04.008] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 03/03/2014] [Accepted: 04/10/2014] [Indexed: 12/14/2022]
Abstract
Human genomic DNA is in a dynamic balance of damage and repair. Cells employ multiple and specific repair pathways, such as nucleotide excision repair (NER), as unrepaired DNA damage has deleterious consequences and could give rise to carcinogenesis. Gene polymorphisms play a crucial role in predicting the risk and prognosis of cancer. Polymorphisms of NER-related genes could alter the ability of NER to effectively monitor and repair DNA damage, and thus may be associated with genetic susceptibility, chemotherapeutic sensitivity and prognosis of cancer. In recent years, increasing studies have focused on the association between polymorphisms of NER genes and gastric cancer, the world's fourth most common cancer and the second most common cause for cancer-related death. Here we reviewed the recent studies on the associations between polymorphisms of NER genes and gastric cancer from perspectives of genetic susceptibility, chemotherapeutic sensitivity and prognosis.
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Affiliation(s)
- Jingwei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Caiyun He
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China
| | - Chengzhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.
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Hui L, Liping G, Jian Y, Laisui Y. A new design without control population for identification of gastric cancer-related allele combinations based on interaction of genes. Gene 2014; 540:32-6. [PMID: 24582974 DOI: 10.1016/j.gene.2014.02.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Revised: 01/31/2014] [Accepted: 02/17/2014] [Indexed: 01/17/2023]
Abstract
OBJECTIVE The purpose of this study was to develop a novel approach without control population to examine the relationship between the presence of specific allele combinations at different loci with the onset of gastric cancer. METHODS DNA samples were collected from patients with gastric cancer. Alleles from short tandem repeat loci were determined using the STR Profiler Plus PCR amplification kit (15 STR loci). The observed and expected frequencies of specific allele combinations were calculated; statistically significant allele combinations were identified by comparing the observed frequency with the expected frequency. The age at disease onset of patients carrying a specific allele combination was further analysed; allele combinations related to the gastric cancer were effectively identified from the large number of possible allele combinations by cross-validation of the 2 sets of analytical results. RESULTS A total of 2209 pairwise combinations were obtained by computer counting, of which 11 pairs of genes showed significant differences between the observed and expected frequencies (p<0.05). The p value for the cross-validation was also less than 0.05 for 2 pair of alleles (D8S1179-16 and D5S818-13; D2S1338-23 and D6S1043-11). CONCLUSION Gastric cancer onset may be associated with these allele combinations. The new methodology without control group will enable additional discoveries pertaining to the relationship between specific allele combinations at different loci and the onset of complex diseases.
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Affiliation(s)
- Liu Hui
- College of Medical Laboratory, Dalian Medical University, China.
| | - Gai Liping
- Dept. of Physics, Dalian Medical University, China
| | - Yu Jian
- College of Medical Laboratory, Dalian Medical University, China
| | - Yu Laisui
- College of Medical Laboratory, Dalian Medical University, China
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Meta-analysis of the association of glutathione S-transferase T1 null/presence gene polymorphism with the risk of gastric carcinoma. Mol Biol Rep 2013; 41:639-49. [PMID: 24352702 DOI: 10.1007/s11033-013-2902-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2013] [Accepted: 12/10/2013] [Indexed: 12/23/2022]
Abstract
A possible association of glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and an increased risk of developing gastric carcinoma is still unclear and hotly debated. This investigation was performed to assess the association of the GSTT1 null/presence gene polymorphism with the risk of gastric carcinoma via a meta-analysis to increase sample size and statistical significance. PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) were searched on March 1, 2013, association reports were identified, and eligible studies were recruited and synthesized. Fifty-two reports were found to be suitable for this meta-analysis for the association of the GSTT1 null genotype with gastric carcinoma risk. The results showed that there was a significantly increased gastric carcinoma risk when the GSTT1 null genotype was present in the overall population (OR 1.21, 95 % CI 1.11-1.32, P < 0.0001), Caucasians (OR 1.25, 95 % CI 1.05-1.48, P = 0.01), East-Asians (OR 1.18, 95 % CI 1.06-1.31, P = 0.003), and Chinese (OR 1.24, 95 % CI 1.07-1.44, P = 0.005). However, no statistically relevant association could be established for the Indian ethnic group (OR 1.33, 95 % CI 0.94-1.90, P = 0.11). In conclusion, the GSTT1 null genotype is associated with an increased gastric carcinoma risk in the overall population, Caucasians, East-Asians, and Chinese.
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