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Nayerpour Dizaj T, Doustmihan A, Sadeghzadeh Oskouei B, Akbari M, Jaymand M, Mazloomi M, Jahanban-Esfahlan R. Significance of PSCA as a novel prognostic marker and therapeutic target for cancer. Cancer Cell Int 2024; 24:135. [PMID: 38627732 PMCID: PMC11020972 DOI: 10.1186/s12935-024-03320-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 03/30/2024] [Indexed: 04/20/2024] Open
Abstract
One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers.
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Affiliation(s)
- Tina Nayerpour Dizaj
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolfazl Doustmihan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behnaz Sadeghzadeh Oskouei
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Akbari
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Jaymand
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - MirAhmad Mazloomi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rana Jahanban-Esfahlan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Mehrotra R, Tulsyan S, Hussain S, Mittal B, Singh Saluja S, Singh S, Tanwar P, Khan A, Javle M, Hassan MM, Pant S, De Aretxabala X, Sirohi B, Rajaraman P, Kaur T, Rath GK. Genetic landscape of gallbladder cancer: Global overview. MUTATION RESEARCH. REVIEWS IN MUTATION RESEARCH 2018; 778:61-71. [PMID: 30454684 DOI: 10.1016/j.mrrev.2018.08.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 08/17/2018] [Accepted: 08/22/2018] [Indexed: 12/13/2022]
Abstract
Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed.
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Affiliation(s)
- Ravi Mehrotra
- Division of Preventive Oncology, National Institute of Cancer Prevention and Research, Noida, India.
| | - Sonam Tulsyan
- Division of Preventive Oncology, National Institute of Cancer Prevention and Research, Noida, India
| | - Showket Hussain
- Division of Molecular Oncology, National Institute of Cancer Prevention and Research, Noida, India
| | - Balraj Mittal
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | - Sundeep Singh Saluja
- Department of Surgical Gastroenterology & Hepatology, GB Pant Hospital, New Delhi, India
| | - Sandeep Singh
- Clinical Epidemiology, Biostatics and Bioinformatics Academic Medical Center, Amsterdam, Netherlands
| | - Pranay Tanwar
- Laboratory Oncology Unit, Rotary Cancer Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Asiya Khan
- Laboratory Oncology Unit, Rotary Cancer Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Centre, USA
| | - Manal M Hassan
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, MD Anderson Cancer Centre, USA
| | - Shubham Pant
- Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, MD Anderson Cancer Centre, USA
| | | | - Bhawna Sirohi
- New India Cancer Charity Initiative, Research and Education in Cancer and Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
| | - Preetha Rajaraman
- U.S. Health Attache, India & Regional Representative, South Asia, Office of Global Affairs, DHHS, New Delhi, Delhi, India
| | | | - G K Rath
- Laboratory Oncology Unit, Rotary Cancer Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
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Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol 2017; 23:3978-3998. [PMID: 28652652 PMCID: PMC5473118 DOI: 10.3748/wjg.v23.i22.3978] [Citation(s) in RCA: 259] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Revised: 02/01/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.
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Association between PSCA gene polymorphisms and the risk of cancer: an updated meta-analysis and trial sequential analysis. Oncotarget 2017; 8:51766-51778. [PMID: 28881685 PMCID: PMC5584286 DOI: 10.18632/oncotarget.17011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 03/30/2017] [Indexed: 01/25/2023] Open
Abstract
Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.
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Wang M, Wang X, Fu SW, Liu X, Jin T, Kang H, Ma X, Lin S, Guan H, Zhang S, Liu K, Dai C, Zhu Y, Dai Z. Single-nucleotide polymorphisms in PSCA and the risk of breast cancer in a Chinese population. Oncotarget 2016; 7:27665-27675. [PMID: 27050280 PMCID: PMC5053679 DOI: 10.18632/oncotarget.8491] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 03/18/2016] [Indexed: 01/02/2023] Open
Abstract
This study explored the associations between common PSCA single-nucleotide polymorphisms (rs2294008, rs2978974, and rs2976392) and breast cancer among 560 breast cancer cases and 583 controls (Chinese Han women). We found rs2294008 was significantly associated with a high risk of breast cancer (homozygote model, odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.06-2.59; recessive, OR: 1.64, 95% CI: 1.06-2.53). And stratification by menopausal status revealed an association of the minor allele of rs2294008 with breast cancer risk among premenopausal (homozygote model, OR: 2.41, 95% CI: 1.03-5.66; recessive, OR: 2.80, 95 % CI: 1.21-6.47) and postmenopausal women (allele model, OR: 1.29, 95% CI: 1.01-1.65). Rs2978974 influenced the breast cancer risk among postmenopausal women in heterozygote model (OR: 1.47, 95% CI: 1.05-2.07). When stratified by clinicopathologic features, the T allele of rs2294008 was associated with progesterone receptor status (homozygote model, OR: 1.98, 95% CI: 1.08-3.63; recessive, OR: 1.87, 95% CI: 1.04-3.37), and the rs2976392 polymorphism was associated with high lymph node metastasis risk in homozygote model (OR: 2.09, 95%CI: 1.01-4.31). Further haplotype analysis suggested that Trs2294008 Ars2976392 Grs2978974 haplotype enhances breast cancer risk (OR:1.52, 95%CI:1.23-1.89, P<0.001). Therefore, among Chinese Han women, the PSCA rs2294008, rs2978974, and rs2976392 minor alleles are associated with increased breast cancer risk especially in progesterone receptor positive breast cancer patients, with breast cancer risk in postmenopausal women, and with high lymph node metastasis risk, respectively. Moreover, Trs2294008 Ars2976392 Grs2978974 haplotype was associated with significantly increased risk of breast cancer.
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Affiliation(s)
- Meng Wang
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Xijing Wang
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Sidney W Fu
- Division of Genomic Medicine/Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA
| | - Xinghan Liu
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Tianbo Jin
- National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an 710069, China
| | - Huafeng Kang
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Xiaobin Ma
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Shuai Lin
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Haitao Guan
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Shuqun Zhang
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Kang Liu
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Cong Dai
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Yuyao Zhu
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Zhijun Dai
- Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- Division of Genomic Medicine/Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA
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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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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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Saeki N, Ono H, Yanagihara K, Aoyagi K, Sasaki H, Sakamoto H, Yoshida T. rs2294008T, a risk allele for gastric and gallbladder cancers, suppresses the PSCA promoter by recruiting the transcription factor YY1. Genes Cells 2015; 20:382-91. [PMID: 25727947 DOI: 10.1111/gtc.12228] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 12/31/2014] [Indexed: 12/12/2022]
Abstract
Previous genomewide association studies identified prostate stem cell antigen (PSCA) as a gastric cancer (GC) susceptibility gene and showed an association between GC and the T allele of the single nucleotide polymorphism rs2294008 (C/T) in this gene. The protein product of this gene inhibits cell growth, and the T allele significantly suppresses the transcriptional activity of the -3.2 kb PSCA upstream region. However, the mechanism remains unknown. In this study, we conducted reporter assays using the PSCA upstream region containing the C allele and identified the region from -200 to +38 bp of the transcription initiation site of the gene as a critical region of the -3.2 kb PSCA upstream region. We found that introducing the T allele at rs2294008 generated a consensus binding sequence for the Polycomb group transcription factor Yin Yang 1 (YY1) and that disruption of the consensus sequence restored the transcriptional activity to the -3.2 kb PSCA upstream region. These findings imply that the T allele significantly suppresses PSCA expression in vivo by recruiting YY1 to its promoter, which eventually predisposes gastric epithelial cells to GC development.
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Affiliation(s)
- Norihisa Saeki
- Division of Genetics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan
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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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Rai R, Sharma KL, Misra S, Kumar A, Mittal B. PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females. Gene 2013; 530:172-177. [PMID: 23988503 DOI: 10.1016/j.gene.2013.08.058] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 08/01/2013] [Accepted: 08/17/2013] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population. METHODOLOGY A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons. RESULTS No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25). CONCLUSIONS These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.
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Affiliation(s)
- Rajani Rai
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India
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