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Impact of PSCA gene polymorphisms in modulating gastric cancer risk in the Chinese population. Biosci Rep 2019; 39:BSR20181025. [PMID: 31416884 PMCID: PMC6722488 DOI: 10.1042/bsr20181025] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 06/23/2019] [Accepted: 08/13/2019] [Indexed: 12/15/2022] Open
Abstract
Previous studies have identified the prostate stem cell antigen (PSCA) gene rs2294008 C > T and rs2976392 G > A polymorphisms to be associated with the risk of gastric cancer, the results of which are inconsistent. The present study aimed to evaluate the association between the two polymorphisms and the gastric cancer risk in the Chinese population. A hospital-based case-control study was conducted on 549 cases and 592 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the association of the two polymorphisms on the gastric cancer risk. We found that both rs2294008 (CT vs. CC, OR = 1.55, 95% CI = 1.20-1.99, P<0.001 and CT+TT vs. CC, OR = 1.38, 95% CI = 1.09-1.74, P=0.008) and rs2976392 (GA vs. GG, OR = 1.61, 95% CI = 1.25-2.07, P<0.001 and GA+AA vs. GG, OR = 1.52, 95% CI = 1.20-1.92, P<0.001) were associated with an increased gastric cancer. In the combined analysis of the two polymorphisms, subjects with more than one risk genotype have a significantly increased risk of gastric cancer (OR = 1.38, 95% CI = 1.09-1.75, P=0.008) in comparison with those without any risk genotypes. In conclusion, our findings verified that the PSCA gene rs2294008 and rs2976392 polymorphisms were both significantly associated with an increased risk of gastric cancer in the Chinese population. Well-designed functional studies are to be warranted to confirm these findings.
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Sung H, Hu N, Yang HH, Giffen CA, Zhu B, Song L, Su H, Wang C, Parisi DM, Goldstein AM, Taylor PR, Hyland PL. Association of high-evidence gastric cancer susceptibility loci and somatic gene expression levels with survival. Carcinogenesis 2017; 38:1119-1128. [PMID: 29028942 DOI: 10.1093/carcin/bgx090] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 08/17/2017] [Indexed: 12/17/2022] Open
Abstract
Eleven high-evidence single-nucleotide polymorphisms (SNPs) at nine loci for gastric cancer (GC) risk were reported, but their associations with survival remain unknown. In this study, we examined associations between SNP and GC survival by anatomic location and histology among 1147 incident cases from the Shanxi Upper Gastrointestinal Genetics Project. We further examined whether SNPs were expression quantitative trait loci in normal and tumor gastric tissues, and whether tumor versus normal somatic mRNA differences in 126 cases were associated with survival. No SNPs were associated with GC survival overall. However, subtype-specific associations were observed for gastric cardia adenocarcinomas at MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC = 1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3 rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04). Rs2294008T was a cis-expression quantitative trait loci for PSCA, upregulating mRNA in normal gastric (β = 0.60; P = 5.7E-21) and GC (β = 0.30; P = 0.0089) tissues. Cases in the highest quartile (the smallest downregulation of tumor PSCA) had shortest survival than cases with the most downregulated PSCA (median survival of 0.47 years in the highest quartile versus 3.73 years in the lowest quartile; hazard ratio = 9.70; 95% CI = 2.46-38.4; P = 0.0012). Less striking effects for mRNA levels were observed for MTX1 at 1q22 in gastric cardia adenocarcinoma and for JRK at 8q24.3 in diffuse GC. Our results suggest three high-evidence GC risk loci have prognostic importance in GC subtypes. Future studies in well-characterized independent populations are warranted to validate our findings and further investigate the clinical utility of these variants in predicting GC prognosis.
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Affiliation(s)
- Hyuna Sung
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Nan Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Howard H Yang
- High-dimension Data Analysis Group, Basic Research Laboratory, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA
| | - Carol A Giffen
- Information Management Services, Inc, Calverton, MD, USA
| | - Bin Zhu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Lei Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Hua Su
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Chaoyu Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | | | - Alisa M Goldstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Paula L Hyland
- Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA
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Gigek CO, Calcagno DQ, Rasmussen LT, Santos LC, Leal MF, Wisnieski F, Burbano RR, Lourenço LG, Lopes-Filho GJ, Smith MAC. Genetic variants in gastric cancer: Risks and clinical implications. Exp Mol Pathol 2017; 103:101-111. [PMID: 28736214 DOI: 10.1016/j.yexmp.2017.07.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 07/03/2017] [Accepted: 07/19/2017] [Indexed: 12/14/2022]
Abstract
Cancer is a multifactorial disease that involves many molecular alterations. Gastric cancer (GC) is the third leading cause of cancer death worldwide. GC is a highly heterogeneous disease with different molecular and genetics features. Therefore, this review focuses on an overview of the genetic aspects of gastric cancer by highlighting the important impact and role of deletions and/or duplications of chromosomal segments, genomic variants, H. pylori infection and interleukin variants, as found in gene expression and newly proposed molecular classification studies. The challenge is to better understand the mechanisms and different pathways that lead to the development and progression of GC.
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Affiliation(s)
- Carolina Oliveira Gigek
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil; Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil.
| | - Danielle Queiroz Calcagno
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará (UFPA), CEP: 66073-000 Belém, Pará, Brazil
| | | | - Leonardo Caires Santos
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
| | - Mariana Ferreira Leal
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil; Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo (UNIFESP), CEP 04038-032 São Paulo, Brazil
| | - Fernanda Wisnieski
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
| | | | - Laercio Gomes Lourenço
- Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil
| | - Gaspar Jesus Lopes-Filho
- Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil
| | - Marilia Arruda Cardoso Smith
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
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Kaveh F, Baumbusch LO, Nebdal D, Børresen-Dale AL, Lingjærde OC, Edvardsen H, Kristensen VN, Solvang HK. A systematic comparison of copy number alterations in four types of female cancer. BMC Cancer 2016; 16:913. [PMID: 27876019 PMCID: PMC5120489 DOI: 10.1186/s12885-016-2899-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 10/30/2016] [Indexed: 01/06/2023] Open
Abstract
Background Detection and localization of genomic alterations and breakpoints are crucial in cancer research. The purpose of this study was to investigate, in a methodological and biological perspective, different female, hormone-dependent cancers to identify common and diverse DNA aberrations, genes, and pathways. Methods In this work, we analyzed tissue samples from patients with breast (n = 112), ovarian (n = 74), endometrial (n = 84), or cervical (n = 76) cancer. To identify genomic aberrations, the Circular Binary Segmentation (CBS) and Piecewise Constant Fitting (PCF) algorithms were used and segmentation thresholds optimized. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was applied to the segmented data to identify significantly altered regions and the associated genes were analyzed by Ingenuity Pathway Analysis (IPA) to detect over-represented pathways and functions within the identified gene sets. Results and Discussion Analyses of high-resolution copy number alterations in four different female cancer types are presented. For appropriately adjusted segmentation parameters the two segmentation algorithms CBS and PCF performed similarly. We identified one region at 8q24.3 with focal aberrations that was altered at significant frequency across all four cancer types. Considering both, broad regions and focal peaks, three additional regions with gains at significant frequency were revealed at 1p21.1, 8p22, and 13q21.33, respectively. Several of these events involve known cancer-related genes, like PPP2R2A, PSCA, PTP4A3, and PTK2. In the female reproductive system (ovarian, endometrial, and cervix [OEC]), we discovered three common events: copy number gains at 5p15.33 and 15q11.2, further a copy number loss at 8p21.2. Interestingly, as many as 75% of the aberrations (75% amplifications and 86% deletions) identified by GISTIC were specific for just one cancer type and represented distinct molecular pathways. Conclusions Our results disclose that some prominent copy number changes are shared in the four examined female, hormone-dependent cancer whereas others are definitive to specific cancer types. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2899-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Fatemeh Kaveh
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.,Medical Genetics Department, Oslo University Hospital Ullevål, Oslo, Norway.,Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Lars O Baumbusch
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.,Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Daniel Nebdal
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
| | - Anne-Lise Børresen-Dale
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
| | - Ole Christian Lingjærde
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.,Department of Computer Science, University of Oslo, Oslo, Norway
| | - Hege Edvardsen
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
| | - Vessela N Kristensen
- Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. .,Department of Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, Lørenskog, Norway.
| | - Hiroko K Solvang
- Marine Mammals Research Group, Institute of Marine Research, Bergen, Norway
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Skierucha M, Milne ANA, Offerhaus GJA, Polkowski WP, Maciejewski R, Sitarz R. Molecular alterations in gastric cancer with special reference to the early-onset subtype. World J Gastroenterol 2016; 22:2460-2474. [PMID: 26937134 PMCID: PMC4768192 DOI: 10.3748/wjg.v22.i8.2460] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 11/06/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
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Chandra V, Kim JJ, Gupta U, Mittal B, Rai R. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population. Genes (Basel) 2016; 7:9. [PMID: 26891331 PMCID: PMC4773753 DOI: 10.3390/genes7020009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 02/01/2016] [Accepted: 02/04/2016] [Indexed: 12/12/2022] Open
Abstract
Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, p ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk.
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Affiliation(s)
- Vishal Chandra
- Department of Biosciences, Integral University, Lucknow 226026 (Uttar Pradesh), India.
| | - Jong Joo Kim
- School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea.
| | - Usha Gupta
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014 (Uttar Pradesh), India.
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014 (Uttar Pradesh), India.
| | - Rajani Rai
- School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea.
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Rai R, Kim JJ, Misra S, Kumar A, Mittal B. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations. Int J Mol Sci 2015; 16:28038-28049. [PMID: 26602921 PMCID: PMC4691025 DOI: 10.3390/ijms161226077] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Revised: 11/12/2015] [Accepted: 11/13/2015] [Indexed: 12/16/2022] Open
Abstract
Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.
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Affiliation(s)
- Rajani Rai
- School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea.
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow-226014, India.
| | - Jong Joo Kim
- School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Korea.
| | - Sanjeev Misra
- Department of Surgical Oncology, King George's Medical University (KGMU), Lucknow-226003, India.
| | - Ashok Kumar
- Department of Surgical Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow-226014, India.
| | - Balraj Mittal
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow-226014, India.
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Geng P, Li J, Wang N, Ou J, Xie G, Liu C, Zhao X, Xiang L, Liao Y, Liang H. PSCA rs2294008 Polymorphism with Increased Risk of Cancer. PLoS One 2015; 10:e0136269. [PMID: 26308216 PMCID: PMC4550426 DOI: 10.1371/journal.pone.0136269] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 08/03/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Published data on the association between PSCA rs2294008 polymorphism and cancer risk have implicated inconclusive results. To determine the relationship and to precisely assess the effect size estimate of the association, we performed a meta-analysis. METHODS We searched published literature in Embase and PubMed databases using the search terms "PSCA", "prostate stem cell antigen", "variants", "polymorphism", "polymorphisms", and "cancer". A total of 21 eligible articles were retrieved, with 27, 197 cancer cases and 48, 237 controls. RESULTS On the whole, we found the association between PSCA rs2294008 polymorphism and cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to 1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14, 95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR = 1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity showed similar results. CONCLUSIONS Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer.
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Affiliation(s)
- Peiliang Geng
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Jianjun Li
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Ning Wang
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Juanjuan Ou
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Ganfeng Xie
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Chen Liu
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Xiaoxin Zhao
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Lisha Xiang
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Yunmei Liao
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
| | - Houjie Liang
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China
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9
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Gu Y, Dai QS, Hua RX, Zhang B, Zhu JH, Huang JW, Xie BH, Xiong SQ, Tan GS, Li HP. PSCA s2294008 C>T and rs2976392 G>A polymorphisms contribute to cancer susceptibility: evidence from published studies. Genes Cancer 2015; 6:254-264. [PMID: 26124924 PMCID: PMC4482246 DOI: 10.18632/genesandcancer.63] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2015] [Accepted: 04/27/2015] [Indexed: 12/17/2022] Open
Abstract
PSCA gene plays an important role in cell adhesion, proliferation and survival. Increasing studies have focused on the association of PSCA gene rs2294008 C>T and rs2976392 G>A with cancer risk. However, the conclusions were inconsistent. Therefore, we performed a meta-analysis to elucidate whether there is a true association, or artifact. We systematically searched eligible studies from MEDLINE, EMBASE and CBM database. Odds ratios and 95% confidence intervals were used to evaluate the strength of the association. The final analysis included 32 studies consisting of 30028 cases and 38765 controls for the rs2294008 C>T polymorphism, and 14 studies with 8190 cases and 7176 controls for the rs2976392 G>A polymorphism. Consequently, the PSCA rs2294008 C>T polymorphism was significantly associated with increased overall cancer risk. Further stratifications indicated the increased risk was more pronounced for gastric (diffused type and non-gastric cardia adenocarcinoma) and bladder cancer. A similar association was observed for the rs2976392 G>A polymorphism. This meta-analysis demonstrated that both of the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms are associated with increased cancer risk, especially for gastric cancer and bladder cancer. Further large-scale studies with different ethnicities and subtypes of gastric cancer are required to confirm the results from this meta-analysis.
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Affiliation(s)
- Yong Gu
- Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qiang-Sheng Dai
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Rui-Xi Hua
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bing Zhang
- Department of Medical Imaging, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jin-Hong Zhu
- Molecular Epidemiology Laboratory and Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Jian-Wen Huang
- Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Bin-Hui Xie
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, China
| | - Shi-Qiu Xiong
- Department of Biochemistry, University of Leicester, Leicester, UK
| | - Guo-Sheng Tan
- Department of Medical Imaging, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - He-Ping Li
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.,Department of Medical Imaging, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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10
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Wang M, Wang XJ, Ma YF, Ma XB, Dai ZM, Lv Y, Lin S, Liu XH, Yang PT, Dai ZJ. PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk. Ther Clin Risk Manag 2015; 11:237-245. [PMID: 25709466 PMCID: PMC4335611 DOI: 10.2147/tcrm.s77089] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case-control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. METHODS The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. RESULTS Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08-1.28; TT vs CC, OR: 1.36, 95% CI: 1.14-1.62; TC vs CC, OR: 1.29, 95% CI: 1.17-1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18-1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02-1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. CONCLUSION Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer.
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Affiliation(s)
- Meng Wang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xi-Jing Wang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Yun-Feng Ma
- Department of Immunology and Pathogenic Biology, Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xiao-Bin Ma
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Zhi-Ming Dai
- Department of Hematology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Ye Lv
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Shuai Lin
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Xing-Han Liu
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Peng-Tao Yang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
| | - Zhi-Jun Dai
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China
- Center for Translational Medicine, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China
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Sun H, Wu X, Wu F, Li Y, Yu Z, Chen X, Chen Y, Yang W. Associations of genetic variants in the PSCA, MUC1 and PLCE1 genes with stomach cancer susceptibility in a Chinese population. PLoS One 2015; 10:e0117576. [PMID: 25658482 PMCID: PMC4319726 DOI: 10.1371/journal.pone.0117576] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2014] [Accepted: 12/27/2014] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Several genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs). METHODS To evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings. RESULTS In the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07-1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03-1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02-1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00-1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15-1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14-1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60-0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03-1.64), when compared with those having 0-1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer. CONCLUSIONS This study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.
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Affiliation(s)
- Hongwei Sun
- Department of Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Xiaoli Wu
- Department of Gastroenterology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Fang Wu
- Department of Gastroenterology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Ying Li
- Department of Operating room, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Zhengping Yu
- Department of Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Xiangrong Chen
- Department of Gastroenterology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Yunzhi Chen
- Department of Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
| | - Wenjun Yang
- Department of Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China
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Abstract
Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality. This cancer is also associated with poor survival rates. Understanding the genetic basis of gastric cancer will offer insights into its pathogenesis, help identify new biomarkers and novel treatment targets, aid prognostication and could be central to developing individualized treatment strategies in the future. An inherited component contributes to <3% of gastric cancers; the majority of genetic changes associated with gastric cancer are acquired. Over the past few decades, advances in technology and high-throughput analysis have improved understanding of the molecular aspects of the pathogenesis of gastric cancer. These aspects are multifaceted and heterogeneous and represent a wide spectrum of several key genetic influences, such as chromosomal instability, microsatellite instability, changes in microRNA profile, somatic gene mutations or functional single nucleotide polymorphisms. These genetic aspects of the pathogenesis of gastric cancer will be addressed in this Review.
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Affiliation(s)
- Mairi H McLean
- National Cancer Institute, Laboratory of Molecular Immunoregulation, Cancer &Inflammation Program, 1050 Boyles Street, Frederick, MD 21702-1201, USA
| | - Emad M El-Omar
- Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB51 5ER, UK
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Rizzato C, Kato I, Plummer M, Muñoz N, Canzian F. Genetic variation in PSCA and risk of gastric advanced preneoplastic lesions and cancer in relation to Helicobacter pylori infection. PLoS One 2013; 8:e73100. [PMID: 24023815 PMCID: PMC3762831 DOI: 10.1371/journal.pone.0073100] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 07/18/2013] [Indexed: 01/09/2023] Open
Abstract
SNPs in the Prostate Stem Cell Antigen (PSCA) gene have been found associated with gastric cancer (GC) risk in a genome-wide association study. This association has been replicated in several populations. In this study we assessed the impact of PSCA genotype on the risk of advanced gastric precancerous lesions and GC. We used baseline gastric histopathology data and DNA from frozen gastric biopsies of 2045 subjects enrolled in a chemoprevention trial for gastric precancerous lesions in Venezuela, and 180 cases of GC from the same area. We analyzed 3 SNPs in the PSCA gene (rs2294008, rs9297976 and rs12155758) which were previously found to be associated with GC risk in Europeans. The T allele of rs2294008 was found to be associated with a higher prevalence of atrophic gastritis (OR = 1.44; 95% CI 1.03-2.01 for the dominant model) and intestinal metaplasia (OR = 1.50; 95% CI 1.13-1.98 for the dominant model). We also confirmed the association with higher risk of gastric cancer (OR = 2.34; 95% CI 1.36-4.01 for the allele carriers). SNP rs12155758 was not associated with risk of gastric preneoplastic lesions, but we confirmed its association with higher GC risk (OR 1.95; 95% CI 1.29-2.97 for dominant model). We tested the relevance of the presence of the Helicobacter pylori cagA gene, which is known to increase the risk of more severe gastric lesions, but we did not find any clearcut interaction with PSCA SNPs in defining risk of gastric precancerous lesions or cancer.
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Affiliation(s)
| | - Ikuko Kato
- Wayne State University, Departments of Oncology and Pathology, Detroit, Michigan, United States of America
| | - Martyn Plummer
- International Agency for Research on Cancer (IARC), Lyon, France
| | - Nubia Muñoz
- National Cancer Institute of Colombia, Bogotá, Colombia
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