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Jia L, Wang M, Duan S, Chen J, Zhao M, Ji S, Lv B, Jiang X, He G, Yang J. Genetic history of esophageal cancer group in southwestern China revealed by Y-chromosome STRs and genomic evolutionary connection analysis. Heliyon 2024; 10:e29867. [PMID: 38720733 PMCID: PMC11076658 DOI: 10.1016/j.heliyon.2024.e29867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 05/12/2024] Open
Abstract
Genetic and environmental factors play crucial roles in the development of esophageal cancer (EC) and contribute uniquely or cooperatively to human cancer susceptibility. Sichuan is located in the interior of southwestern China, and the northern part of Sichuan is one of the regions with a high occurrence of EC. However, the factors influencing the high incidence rate of EC in the Sichuan Han Chinese population and its corresponding genetic background and origins are still poorly understood. Here, we utilized genome-wide single nucleotide polymorphisms (SNPs) and Y-chromosome short tandem repeats (Y-STRs) to characterize the genetic structure, connection, and origin of cancer groups and general populations. We generated Y-STR-based haplotype data from 214 Sichuan individuals, including the Han Chinese EC population and a control group of Han Chinese individuals. Our results, obtained from Y-STR-based population statistical methods (analysis of molecular variance (AMOVA), principal component analysis (PCA), and phylogenetic analysis), demonstrated that there was a genetic substructure difference between the EC population in the high-incidence area of northern Sichuan Province and the control population. Additionally, there was a strong genetic relationship between the EC population in the northern Sichuan high-incidence area and those at high risk in both the Fujian and Chaoshan areas. In addition, we obtained high-density SNP data from saliva samples of 60 healthy Han Chinese individuals from three high-prevalence areas of EC in China: Sichuan Nanchong, Fujian Quanzhou, and Henan Xinxiang. As inferred from the allele frequency of SNPs and sharing patterns of haplotype segments, the evolutionary history and admixture events suggested that the Han population from Nanchong in northern Sichuan Province shared a close genetic relationship with the Han populations from Xinxiang in Henan Province and Quanzhou in Fujian Province, both of which are regions with a high prevalence of EC. Our study illuminated the genetic profile and connection of the Northern Sichuan Han population and enriched the genomic resources and features of the Han Chinese populations in China, especially for the Y-STR genetic data of the Han Chinese EC population. Populations living in different regions with high incidences of EC may share similar genetic backgrounds, which offers new insights for further exploring the genetic mechanisms underlying EC.
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Affiliation(s)
- Lihua Jia
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
| | - Mengge Wang
- Center for Archaeological Science, Sichuan University, Chengdu, 610000, China
- Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China
| | - Shuhan Duan
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
- Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China
| | - Jianghua Chen
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
| | - Mei Zhao
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
| | - Simeng Ji
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China
| | - Bingbing Lv
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China
| | - Xiucheng Jiang
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
- Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China
| | - Guanglin He
- Center for Archaeological Science, Sichuan University, Chengdu, 610000, China
- Institute of Rare Diseases, West China Hospital of Sichuan University, Sichuan University, Chengdu, 610000, China
| | - Junbao Yang
- Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal diagnosis, Affiliated Hospital of Northern Sichuan Medical College, Nanchong, Sichuan, 637007, China
- School of Laboratory Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, China
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Li S, Hopper JL. Familial aggregation of esophageal cancer. Chin Med J (Engl) 2023; 136:2644-2646. [PMID: 37925596 PMCID: PMC10617878 DOI: 10.1097/cm9.0000000000002623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Indexed: 04/05/2023] Open
Affiliation(s)
- Shuai Li
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC 3053, Australia
- Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
- Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC 3051, Australia
| | - John L. Hopper
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC 3053, Australia
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Zhang LQ, Du XJ, Zhou FY, Chen PN, Wang HL, Sun L, Li XL. Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2022; 37:994-999. [PMID: 33137207 DOI: 10.1007/s13187-020-01911-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/26/2020] [Indexed: 06/11/2023]
Abstract
The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.
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Affiliation(s)
- Lian Qun Zhang
- Anyang Tumor Hospital, Anyang, 455000, Henan, China
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China
| | - Xian Juan Du
- Anyang Tumor Hospital, Anyang, 455000, Henan, China
| | - Fu You Zhou
- Anyang Tumor Hospital, Anyang, 455000, Henan, China
| | - Pei Nan Chen
- The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, Henan, China
| | - Hai Ling Wang
- The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, Henan, China
| | - Li Sun
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiu Ling Li
- Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.
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Wang C, Cheng L, Song S, Wu S, Sun G. Gli1 interacts with YAP1 to promote tumorigenesis in esophageal squamous cell carcinoma. J Cell Physiol 2020; 235:8224-8235. [PMID: 31957872 DOI: 10.1002/jcp.29477] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 01/08/2020] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC.
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Affiliation(s)
- Chongchong Wang
- Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Li Cheng
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Shasha Song
- Digestive Department, Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Shan Wu
- Department of Oncology, Fourth Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guoping Sun
- Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, China
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Su Z, Zou GR, Mao YP, OuYang PY, Cao XL, Xie FY, Li Q. Prognostic impact of family history of cancer in Southern Chinese patients with esophageal squamous cell cancer. J Cancer 2019; 10:1349-1357. [PMID: 31031844 PMCID: PMC6485237 DOI: 10.7150/jca.26511] [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: 04/05/2018] [Accepted: 12/05/2018] [Indexed: 12/30/2022] Open
Abstract
Background: First degree family history of cancer is associated with developing esophageal cancer and sparse data is about the impact on poor survival among established esophageal squamous cell cancer (ESCC) patients. In this study, we investigated the prognoses of patients with ESCC with a family history. Methods: A total of 479 ESCC patients were retrospectively enrolled from a Southern Chinese institution. A positive family history was defined as having malignant cancer among parents and siblings. Kaplan-Meier plots and Cox proportional hazards regressions were applied for overall survival (OS) and progression-free survival (PFS). Results: Among 479 patients, 119 (24.8%) and 68 (14.2%) reported a first-degree family history of cancer and digestive tract cancer, respectively. Compared with patients without a family history of cancer, the adjusted hazard ratios (HR) among those with it were 1.40 (95% CI, 1.08-1.82, p=0.011) for death, 1.36 (95% CI, 1.05-1.76, p=0.018) for progression. Similar results were observed in those with a family history of digestive tract cancer (HR=1.69, 95%CI, 1.24-1.98, p=0.001 for death and HR=1.77, 95%CI, 1.30-2.37, p<0.001 for progression, respectively). Furthermore, there was a trend for increasing risk of overall mortality (p=0.021, p=0.004, respectively), and progression (p=0.022, p=0.001, respectively) with an increasing number of affected family members. Conclusion: A first-degree family history of cancer, especially digestive tract cancer is associated with poor survival for established ESCC patients and plays an important role in prognosis. The patients with a family history of cancer might need a greater intensity of treatment and more frequent follow-up.
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Affiliation(s)
- Zhen Su
- Panyu central hospital, Cancer Institute of Panyu, Guangzhou, China
| | - Guo-Rong Zou
- Panyu central hospital, Cancer Institute of Panyu, Guangzhou, China
| | - Yan-Ping Mao
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Pu-Yun OuYang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Xiao-Long Cao
- Panyu central hospital, Cancer Institute of Panyu, Guangzhou, China
| | - Fang-Yun Xie
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Qun Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
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Yang W, Li Y, Ning T, Cai H, Chen Z, Dong Y, Ke Y. Polymorphisms in the 5' upstream regulatory region of p21(WAF1/CIP1) and susceptibility to oesophageal squamous cell carcinoma. Sci Rep 2016; 6:22564. [PMID: 26932598 PMCID: PMC4773838 DOI: 10.1038/srep22564] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 02/17/2016] [Indexed: 11/09/2022] Open
Abstract
This study aims to scan the 5'-upstream regulatory region of the p21 gene to identify all putative functional single nucleotide polymorphisms (SNPs) and to evaluate the contribution of p21 variants to oesophageal squamous cell carcinoma (ESCC) in the Chinese Han population. Common SNPs were identified, and both locus-based and haplotype-based association tests were used to evaluate the potential risk of these p21 gene polymorphisms for ESCC. Immunohistochemistry assay was further performed to detect the P21 protein expression in ESCC specimens. Twenty three SNPs were identified and seven Tagging SNPs were chosen to represent all 23 SNPs. Univariate analysis indicated that the rs3829963 C and the rs2395655 G alleles increased susceptibility to ESCC (OR = 1.606 and OR = 1.572, respectively). The rs3829963 C and rs2395655 G alleles, combined with cigarette smoking, could further increase the risk for ESCC (OR = 2.657 and OR = 2.828, respectively). Additionally, the rs2395655 G allele appeared to elevate the positive rate of P21 expression in ESCC tissues, as compared to the A allele. This report demonstrates for the first time that rs3829963 and rs2395655, in the promoter of the p21 gene are potentially functional, modulating susceptibility to ESCC among the high-risk cigarette-smoking Chinese population.
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Affiliation(s)
- Wenjun Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China.,Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Cancer Institute of the General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, P. R. China
| | - Yong Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China.,Department of Laboratory Animal, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China
| | - Tao Ning
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China
| | - Zhiqiang Chen
- Radiology Department of General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, P. R. China
| | - Ying Dong
- Key Laboratory of Fertility Preservation and Maintenance (Ministry of Education), Cancer Institute of the General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, P. R. China
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Genetics, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, P. R. China
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Hyland PL, Zhang H, Yang Q, Yang HH, Hu N, Lin SW, Su H, Wang L, Wang C, Ding T, Fan JH, Qiao YL, Sung H, Wheeler W, Giffen C, Burdett L, Wang Z, Lee MP, Chanock SJ, Dawsey SM, Freedman ND, Abnet CC, Goldstein AM, Yu K, Taylor PR. Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data. Int J Epidemiol 2016; 45:206-20. [PMID: 26635288 PMCID: PMC4881832 DOI: 10.1093/ije/dyv294] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2015] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Oesophageal cancer is the fourth leading cause of cancer death in China where essentially all cases are histologically oesophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses of genome-wide association study (GWAS) data combined with tissue-specific expression quantitative trait loci (eQTL) analysis and publicly available functional data can identify biological pathways and/or genes enriched with functionally-relevant disease-associated variants. METHOD We used the adaptive multilocus joint test to analyse 1827 pathways containing 6060 genes using GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. We examined the function of risk alleles using in silico and eQTL analyses in oesophageal tissues. RESULTS Associations with ESCC risk were observed for 36 pathways predominantly involved in apoptosis, cell cycle regulation and DNA repair and containing known GWAS-associated genes. After excluding genes with previous GWAS signals, candidate pathways (and genes) for ESCC risk included taste transduction (KEGG_hsa04742; TAS2R13, TAS2R42, TAS2R14, TAS2R46,TAS2R50), long-patch base excision repair (Reactome_pid; POLD2) and the metabolics pathway (KEGG_hsa01100; MTAP, GAPDH, DCTD, POLD2, AMDHD1). We identified and validated CASP8 rs13016963 and IDH2 rs11630814 as eQTLs, and CASP8 rs3769823 and IDH2 rs4561444 as the potential functional variants in high-linkage disequilibrium with these single nucleotide polymorphisms (SNPs), respectively. Further, IDH2 mRNA levels were down-regulated in ESCC (tumour:normal-fold change = 0.69, P = .75E-14). CONCLUSION Agnostic pathway-based analyses and integration of multiple types of functional data provide new evidence for the contribution of genes in taste transduction and metabolism to ESCC susceptibility, and for the functionality of both established and new ESCC risk-related SNPs.
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Affiliation(s)
| | - Han Zhang
- Division of Cancer Epidemiology and Genetics, and
| | - Qi Yang
- Division of Cancer Epidemiology and Genetics, and
| | | | - Nan Hu
- Division of Cancer Epidemiology and Genetics, and
| | - Shih-Wen Lin
- Division of Cancer Epidemiology and Genetics, and
| | - Hua Su
- Division of Cancer Epidemiology and Genetics, and
| | - Lemin Wang
- Division of Cancer Epidemiology and Genetics, and
| | - Chaoyu Wang
- Division of Cancer Epidemiology and Genetics, and
| | - Ti Ding
- Division of Cancer Epidemiology and Genetics, and
| | - Jin-Hu Fan
- Division of Cancer Epidemiology and Genetics, and
| | - You-Lin Qiao
- Division of Cancer Epidemiology and Genetics, and
| | - Hyuna Sung
- Division of Cancer Epidemiology and Genetics, and
| | | | - Carol Giffen
- Division of Cancer Epidemiology and Genetics, and
| | | | - Zhaoming Wang
- Division of Cancer Epidemiology and Genetics, and Division of Cancer Epidemiology and Genetics, and
| | | | | | | | | | | | | | - Kai Yu
- Division of Cancer Epidemiology and Genetics, and
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Zhang J, Jiang Y, Wu C, Cai S, Wang R, Zhen Y, Chen S, Zhao K, Huang Y, Luketich J, Chen H. Comparison of clinicopathologic features and survival between eastern and western population with esophageal squamous cell carcinoma. J Thorac Dis 2015; 7:1780-6. [PMID: 26623101 DOI: 10.3978/j.issn.2072-1439.2015.10.39] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Esophageal squamous cell carcinoma (ESCC) is the major histologic subtype of esophageal cancer, characterized by a high mortality rate and geographic differences in incidences. It is unknown whether there is difference between "eastern" ESCC and "western" ESCC. This study is attempted to demonstrate the hypothesis by comparing ESCC between Chinese residents and Caucasians living in the US. METHODS The data sources of this study are from United States SEER limited-use database and Shanghai Cancer Registries by Shanghai Municipal Center for Disease Control (SMCDC). Consecutive, non-selected patients with pathologically diagnosed ESCC, between January 1, 2002 and December 31, 2006, were included in this analysis. 1-year, 3-year and 5-year survival estimates were computed and compared between two populations. A Cox proportional hazards model was used to determine factors affecting survival differences. RESULTS A total of 1,718 Chinese, 1,624 Caucasians ESCC patients with individual American Joint Commission on Cancer (AJCC) staging information were included in this study. The Caucasian group had a significantly higher proportion of female patients than Chinese (38.24% vs. 18.68% P<0.01). ESCC was diagnosed in Chinese patients at an earlier age and stage than Caucasians. Generally, Chinese patients had similar overall survival rate with Caucasian by both univariate and multivariate analysis. Overall survival was significantly worse only in male Caucasians compared to Chinese patients (median survival time, 12.4 vs. 14.5 months, P<0.01, respectively). CONCLUSIONS ESCC from eastern and western countries might have some different features. These differences need to be taken into account for the management of ESCC patients in different ethnic groups.
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Affiliation(s)
- Jie Zhang
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Yizhou Jiang
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Chunxiao Wu
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Shuang Cai
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Rui Wang
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Ying Zhen
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Sufeng Chen
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Kuaile Zhao
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Yangle Huang
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - James Luketich
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
| | - Haiquan Chen
- 1 Department of Oncology, Fudan University Shanghai Medical College, Shanghai 200032, China ; 2 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 3 Department of Cancer Control & Prevention, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China ; 4 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200032, China ; 5 Department of Radiotherapy, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 6 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh 15213, USA
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Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma. Sci Rep 2015; 5:16038. [PMID: 26526791 PMCID: PMC4630623 DOI: 10.1038/srep16038] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 10/07/2015] [Indexed: 01/29/2023] Open
Abstract
A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk.
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Bhat GA, Shah IA, Rafiq R, Nabi S, Iqbal B, Lone MM, Islami F, Boffetta P, Dar NA. Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India. Br J Cancer 2015; 113:524-32. [PMID: 26125444 PMCID: PMC4522628 DOI: 10.1038/bjc.2015.218] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Revised: 05/11/2015] [Accepted: 05/21/2015] [Indexed: 02/06/2023] Open
Abstract
Background: Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case–control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms. Methods: We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6–9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0–19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6–10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7–8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population. Conclusion: Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association.
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Affiliation(s)
- G A Bhat
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
| | - I A Shah
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
| | - R Rafiq
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
| | - S Nabi
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
| | - B Iqbal
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
| | - M M Lone
- Departments of Radiation Oncology, SK Institute of Medical Sciences, Soura Srinagar, 190011 India
| | - F Islami
- 1] Surveillance and Health Services Research, American Cancer Society, Atlanta, GA, USA [2] Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, 14117 Iran
| | - P Boffetta
- Tisch Cancer Institute and Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, NY, USA
| | - N A Dar
- Department of Biochemistry, University of Kashmir, Srinagar 190006, India
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11
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A link between cold environment and cancer. Tumour Biol 2015; 36:5953-64. [PMID: 25736923 DOI: 10.1007/s13277-015-3270-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Accepted: 02/17/2015] [Indexed: 12/22/2022] Open
Abstract
Many risk factors such as smoking and change of life style have been shown to promote genetic and adaptive epigenetic changes responsible for tumorigenesis. This study brings environmental temperature as a cancer causing factor to light. The cancer mortality rate (CMR) of a country was correlated with 17 different variables. Multivariate analysis of a total of 188 countries found that the average annual temperature (AAT) of a country might have a significant contribution to cancer death when compared with other factors such as alcohol and meat consumption. Univariate analysis found a negative correlation between AAT and CMR. All these countries were categorized into three temperature zones (zone I, -2 to 11.5 °C; number of countries, 38; zone II, 11.6 to 18.6 °C; number of countries, 32; and zone III, 18.7 to 30 °C; number of countries, 118). Out of the top-most 50 countries having the highest CMR, 26 (68.42 %), 10 (31.25 %), and 14 (11.66 %) belong to zone I, zone II, and zone III, respectively. Out of the least 50 countries having the lowest CMR, 1 (2.63 %), 4 (12.5 %), and 45 (37.5 %) belong to zone I, zone II, and zone III, respectively. CMR is low in those countries situated near to the Torrid zone (33(°) N to 23.5(°)S), but it is high for those countries situated away from these two latitudes. These data indicate that cold temperature may have a contribution in increasing tumorigenesis. High metabolic stress, which is the result of maintaining our body temperature against a cold environment, could be the possible cause for the higher cancer mortality.
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12
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MicroRNAs related polymorphisms and genetic susceptibility to esophageal squamous cell carcinoma. Mol Genet Genomics 2014; 289:1123-30. [PMID: 24916311 DOI: 10.1007/s00438-014-0873-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2014] [Accepted: 05/30/2014] [Indexed: 01/30/2023]
Abstract
Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide and the incidence and mortality in China are the highest. The single nucleotide polymorphisms (SNPs) related to microRNAs could lead to alteration in microRNA expression and contribute to the susceptibility of cancer. To evaluate the association between microRNA-related SNPs and EC, a case-control study including 381 patients with esophageal squamous cell carcinoma (ESCC) and 426 gender, age-matched controls was carried out to investigate the genetic susceptibility of five microRNA-related SNPs (rs2910164 in microRNA-146a, rs11614913 in microRNA-196a-2, rs7813 in GEMIN4, rs1595066 and rs16845990 in ErbB4) as well as the interactions of gene-gene and gene-environment in the development of ESCC. Variant homozygote genotype of rs11614913 in microRNA-196a-2 and rs1595066 in ErbB4 were significantly associated with reduced ESCC risk (OR(adjusted): 0.62, 95 % CI: 0.39-0.99 and OR(adjusted): 0.38, 95 % CI: 0.24-0.61). The analysis of haplotypes in ErbB4 gene showed significant increased ESCC risk in G(rs1595066)C(rs16845990) and G(rs1595066)T(rs16845990) haplotypes (OR(adjusted): 1.46, 95 % CI: 1.08-1.99 and OR(adjusted): 1.33, 95 % CI: 1.10-1.62), and inversely reduced ESCC risk in A(rs1595066)C(rs16845990) and A(rs1595066)T(rs16845990) haplotypes with OR (95 % CI) of 0.75 (0.60-0.94) and 0.65 (0.49-0.86), respectively. These findings suggest that the polymorphisms in the microRNA-related genes may affect susceptibility of ESCC in Chinese Han population and the gene-gene interactions play vital roles in the progression on esophageal cancer. Future studies with larger sample and different ethnic populations are required to support and validate our findings.
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13
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Ko JM, Zhang P, Law S, Fan Y, Song YQ, Zhao XK, Wong EHW, Tang S, Song X, Lung ML, Wang LD. Identity-by-descent approaches identify regions of importance for genetic susceptibility to hereditary esophageal squamous cell carcinoma. Oncol Rep 2014; 32:860-70. [PMID: 24890309 DOI: 10.3892/or.2014.3222] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 04/30/2014] [Indexed: 11/05/2022] Open
Abstract
Worldwide, the highest prevalence of esophageal cancer (EC) occurs in Northern China. High-density SNP arrays allow identification of identity-by-descent (IBD) segments in genomic DNAs representative of shared common ancestral regions. We utilized IBD approaches to map susceptibility loci associated with low-penetrance SNPs in high-risk Henan hereditary esophageal squamous cell carcinoma (ESCC) patients. Affymetrix GeneChip Human mapping SNP array IBD analysis was performed in 32 Henan family history-positive (FH+) ESCC patients, 18 Henan healthy unrelated individuals, and 45 Chinese individuals from a CHB HapMap dataset using PLink (scoring IBD segments individually) and Beagle (scoring of shared IBD segments among case/case vs. control/control pairs) software. Both analyses identified longer IBD segment lengths associated with FH+ ESCC compared to controls. However, there was no strong evidence for a genetic founder effect. Pairing IBD analysis with BEAGLE identified 8 critical IBD segments residing at 2q32.1-q32.2, 3p22.3-p22.2, 4q21.1-q21.21, 7p22.2, 8q23.2-q23.3, 10q23.33-q24.1, 14q24.3 and 16q11.2-q12.1, which were more significantly shared among case/case compared to control/control. The shared IBD segments in FH+ ESCC samples with no overlap with control/CHB Hapmap may encompass potential cancer susceptibility loci. Selected targeted genes, PLCE1, GPT2, SIAH1 and CYP2C-18, residing within the IBD segments at 10q23.33-q24.1 and 16q11.2-q12.1, had statistically significant differential expression in primary ESCC tissues and are likely involved in ESCC carcinogenesis. The importance of these IBD segments to the etiology and development of ESCC in high-risk areas requires further study with expanded sample sizes. This is the first report employing the pairing IBD approach for elucidation of the genetic basis of hereditary ESCC in Henan by applying high throughput SNP array analysis.
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Affiliation(s)
- Josephine My Ko
- Department of Clinical Oncology, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - Peng Zhang
- Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Simon Law
- Department of Surgery, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - Yanhui Fan
- Department of Biochemistry, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - You-Qiang Song
- Department of Biochemistry, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - Xue Ke Zhao
- Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Elibe H W Wong
- Department of Clinical Oncology, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - Sa Tang
- Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Xin Song
- Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China
| | - Maria Li Lung
- Department of Clinical Oncology, University of Hong Kong, Hong Kong, SAR, P.R. China
| | - Li Dong Wang
- Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, P.R. China
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Gu H, Qiu W, Shi Y, Chen S, Yin J. Variant alleles of VEGF and risk of esophageal cancer and lymph node metastasis. Biomarkers 2014; 19:252-8. [PMID: 24654773 DOI: 10.3109/1354750x.2014.902997] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Affiliation(s)
- Haiyong Gu
- Department of Cardiothorac Surgery, Affiliated People’s Hospital of Jiangsu University
ZhenjiangP.R. China
| | - Wanshan Qiu
- Department of Cardiothorac Surgery, Children’s Hospital of Fudan University
ShanghaiP.R. China
| | - Yijun Shi
- Department of Cardiothorac Surgery, Affiliated People’s Hospital of Jiangsu University
ZhenjiangP.R. China
| | - Suocheng Chen
- Department of Cardiothorac Surgery, Affiliated People’s Hospital of Jiangsu University
ZhenjiangP.R. China
| | - Jun Yin
- Department of Cardiothorac Surgery, Affiliated People’s Hospital of Jiangsu University
ZhenjiangP.R. China
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15
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Sun Y, Shi N, Lu H, Zhang J, Ma Y, Qiao Y, Mao Y, Jia K, Han L, Liu F, Li H, Lin Z, Li X, Zhao X. ABCC4copy number variation is associated with susceptibility to esophageal squamous cell carcinoma. Carcinogenesis 2014; 35:1941-50. [DOI: 10.1093/carcin/bgu043] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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16
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Yun YX, Wang YP, Wang P, Cui LH, Wang KJ, Zhang JY, Dai LP. CYP1A1 genetic polymorphisms and risk for esophageal cancer: a case-control study in central China. Asian Pac J Cancer Prev 2014; 14:6507-6512. [PMID: 24377558 DOI: 10.7314/apjcp.2013.14.11.6507] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024] Open
Abstract
The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.
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Affiliation(s)
- Yu-Xia Yun
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China E-mail :
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17
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Wang KJ, Yang JX, Shi JC, Deng SY, Cao XQ, Song CH, Wang P. Genetic epidemiological analysis of esophageal cancer in high-incidence areas of China. Asian Pac J Cancer Prev 2014; 15:9859-9863. [PMID: 25520118 DOI: 10.7314/apjcp.2014.15.22.9859] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024] Open
Abstract
Genetic epidemiological studies have shown that genetic susceptibility to esophageal cancer (EC) is an important cause of its high incidence within families in some areas of China. The purpose of this study was to obtain evidence of a genetic basis of EC in Xin-an and Xin-xiang counties in China. Familial aggregation and complex segregation analyses were performed of 79 EC families in these counties. The heritability of EC was examined using Falconer's method and complex segregation analysis was conducted with the SEGREG program in Statistical Analysis for Genetic Epidemiology (SAGE version 5.3.1). The results showed that the distribution of EC in families did not fit well into a binomial distribution. The heritability of EC among first-degree and second- degree relatives was 67.0±7.31% and 43.1%±9.80%, respectively, and the summing up powered heritability was 53.2±6.74%. The segregation ratio was 0.045. Complex segregation analysis showed that the genetic model of EC was additive. The current results provide evidence for an inherited propensity to EC in certain high-risk groups in China, and support efforts to identify the genes that confer susceptibility to this disease.
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Affiliation(s)
- Kai-Juan Wang
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, China E-mail :
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18
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Han Q, Yao F, Zhong C, Zhao H. TRAF6 promoted the metastasis of esophageal squamous cell carcinoma. Tumour Biol 2013; 35:715-21. [DOI: 10.1007/s13277-013-1098-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 08/08/2013] [Indexed: 01/22/2023] Open
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Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma. Br J Cancer 2013; 109:2266-78. [PMID: 24022190 PMCID: PMC3798955 DOI: 10.1038/bjc.2013.548] [Citation(s) in RCA: 142] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 08/15/2013] [Indexed: 12/11/2022] Open
Abstract
Background: HOX transcript antisense RNA (HOTAIR), which is expressed from the homebox C gene (HOXC) locus, is capable of reprogramming chromatin organisation and promoting cancer cell metastasis and can simultaneously bind the polycomb repressive complex 2, which enhances H3K27 trimethylation, and the LSD1-CoREST-REST complex, which is critical for H3K4 demethylation. Clinically, the overexpression of HOTAIR is a powerful predictor of the tumour progression and overall survival in patients with diverse cancers. The relationship between HOTAIR and oesophageal squamous cell carcinoma (ESCC), however, remains unclear. We investigated the role of HOTAIR in the pathogenesis of ESCC. Methods: We used quantitative real-time PCR to determine the level of HOTAIR in ESCC cell lines and 100 ESCC samples from patients; 56 adjacent non-neoplastic tissues were used as controls. We measured the effect of HOTAIR knockdown and overexpression in ESCC cell lines using colony formation assays, anchorage-independent growth assays, the CCK-8 assay, transwell migration and invasion assays, and Annexin V-binding assays. We analysed the growth of ESCC xenograft tumours in nude mice. Changes in the gene expression and methylation levels in ESCC cell lines were analysed using gene expression microarrays and the Infinium HumanMethylation450K BeadChip assay, respectively. Results: The levels of HOTAIR were increased in ESCC cell lines and patient samples compared with the controls; the expression levels correlated with the disease stage and survival time. The knockdown of HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the extracellular matrix in culture, altered cell cycle progression, and increased the sensitivity of the cells to apoptosis. The HOTAIR knockdown reduced cancer cell metastasis in vivo, and the tumours formed by HOTAIR-silenced ESCC cells were smaller, both in size and weight, than the tumours and metastases formed by the shRNA vector control cells in a mouse xenograft model. The results of the gene microarray study showed that HOTAIR reprogrammed the gene expression profile of ESCC cells, and the gene ontology analysis revealed an enrichment in genes that are important for tumorigenesis, such as genes involved in cell migration and the regulation of the cell cycle. Comparing the gene expression profiles and DNA methylation analysis between the KYSE180 and KYSE180_HOTAIR cells revealed that only a small proportion of the methylation changes were correlated with gene expression changes. Conclusion: HOX transcript antisense RNA is upregulated in ESCC cell lines and patient samples, and promotes ESCC cell proliferation and tumour metastasis in mice. The knockdown of HOTAIR resulted in significant changes in gene expression, and data analysis suggested that HOTAIR-mediated gene regulation has a critical role in ESCC progression and is a novel epigenetic molecular target for treating ESCC patients.
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Duan F, Xie W, Cui L, Wang P, Song C, Qu H, Wang K, Zhang J, Dai L. Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: based on published genome-wide association studies in a central Chinese population. Cancer Epidemiol 2013; 37:647-52. [PMID: 23688607 DOI: 10.1016/j.canep.2013.04.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Revised: 04/21/2013] [Accepted: 04/23/2013] [Indexed: 01/09/2023]
Abstract
A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G>T and rs2274224 C>G) of PLCE1 in a population-based case-control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45-5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46-0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (Ptrend=0.005). The Grs17417407Ars2274223Crs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62-0.93), meanwhile the Grs17417407Grs2274223Crs2274224 and Trs17417407Grs2274223Crs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33-2.18 and OR, 2.51; 95% CI, 1.15-2.49). Gene-environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the "high risk group" with 3.67-fold (OR: 3.67, 95% CI: 2.74-4.92), compared to the "low risk group". Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.
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Affiliation(s)
- Fujiao Duan
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, PR China
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Zhu YH, Fu L, Chen L, Qin YR, Liu H, Xie F, Zeng T, Dong SS, Li J, Li Y, Dai Y, Xie D, Guan XY. Downregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Res 2013; 73:2298-309. [PMID: 23436800 DOI: 10.1158/0008-5472.can-12-2663] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Loss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like small GTPase DIRAS1. Downregulation of DIRAS1 occurred in approximately 50% of primary ESCCs where it was associated significantly with advanced clinical stage, lymph node metastasis, and poor overall survival. LOH and promoter methylation analyses suggested that loss of DIRAS1 expression was mediated by epigenetic mechanisms. Functional studies established that ectopic re-expression of DIRAS1 in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation. Mechanistic investigations suggested that DIRAS1 acted through extracellular signal-regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively. Taken together, our results revealed that DIRAS1 has a pivotal function in ESCC pathogenesis, with possible use as a biomarker and intervention point for new therapeutic strategies.
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Affiliation(s)
- Ying-Hui Zhu
- State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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22
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Hyland PL, Freedman ND, Hu N, Tang ZZ, Wang L, Wang C, Ding T, Fan JH, Qiao YL, Golozar A, Wheeler W, Yu K, Yuenger J, Burdett L, Chanock SJ, Dawsey SM, Tucker MA, Goldstein AM, Abnet CC, Taylor PR. Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma. Carcinogenesis 2013; 34:1062-8. [PMID: 23358850 DOI: 10.1093/carcin/bgt030] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.
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Affiliation(s)
- Paula L Hyland
- Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Rockville, MA 20852,
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Wei W, Ji A, Wang J, Wei Z, Lian C, Yang J, Ma L, Ma L, Qin X, Wang LD. Functional single nucleotide polymorphism in C20orf54 modifies susceptibility to esophageal squamous cell carcinoma. Dis Esophagus 2013; 26:97-103. [PMID: 22533825 DOI: 10.1111/j.1442-2050.2012.01339.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The aim of this study was to explore the association of C20orf54 functional single nucleotide polymorphism (SNP) with the susceptibility to esophageal squamous cell carcinoma (ESCC) in a northern China population. The C20orf54 SNP was genotyped by direct sequencing in 240 cancer patients and 198 controls in northern China. The results showed that drinking status, family history of ESCC, and body mass index have great influence on the risk of developing ESCC. The overall genotype frequencies of C20orf54 in ESCC patients have a significant difference with healthy controls (χ(2) = 8.06, P = 0.018). By using C/C genotype as the reference, the C/T genotype showed a significantly decreased risk to the development of ESCC. Thus, compared with the C/C genotype, smokers, drinkers with C/T genotype significantly decreased the risk of developing ESCC. A positive family history of ESCC with C/T and T/T genotype both increased the risk of developing ESCC. Body mass index between 18.5 and 24 with C/T genotype significantly decreased the risk of developing ESCC. The present study suggests that the C20orf54 functional SNP might be associated with a risk of development in ESCC.
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Affiliation(s)
- W Wei
- Central Laboratory, Heping Hospital-Changzhi Medical College, 161 Jie Fang Dong Street, Changzhi, Shanxi Province, China
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Ainiwaer J, Tuerhong A, Hasim A, Chengsong D, Liwei Z, Sheyhidin I. Association of the plasma riboflavin levels and riboflavin transporter (C20orf54) gene statuses in Kazak esophageal squamous cell carcinoma patients. Mol Biol Rep 2012; 40:3769-75. [DOI: 10.1007/s11033-012-2453-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Accepted: 12/18/2012] [Indexed: 01/08/2023]
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Zhou RM, Li Y, Wang N, Liu BC, Chen ZF, Zuo LF. PLC-ε1 gene polymorphisms significantly enhance the risk of esophageal squamous cell carcinoma in individuals with a family history of upper gastrointestinal cancers. Arch Med Res 2012; 43:578-84. [PMID: 23079034 DOI: 10.1016/j.arcmed.2012.09.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Accepted: 09/18/2012] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Phospholipase C epsilon 1 (PLCε1) may regulate cell growth, differentiation, apoptosis and angiogenesis and play an important role in carcinogenesis and the progression of several cancers. This study was designed to validate the association of the PLCε1 rs2274223 single nucleotide polymorphism (SNP) with esophageal squamous cell carcinoma (ESCC) as identified by genome-wide association studies (GWAS) and further assess whether the rs11599672 SNP could affect an individual's susceptibility to ESCC. METHODS These two SNPs were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) in 527 ESCC patients and 527 controls. RESULTS Compared with the rs2274223 SNP AA genotype, other genotypes or combined genotypes all enhanced the risk of ESCC. Further analyses showed that AG/GG genotype carriers with a family history of upper gastrointestinal cancers (UGIC) had an increased risk of ESCC than those AA genotype carriers without UGIC family history (OR = 2.10, 95% CI = 1.46-3.10). Overall, rs11599672 SNP had no influence on ESCC susceptibility. However, UGIC family history elevated the risk of ESCC for subjects with the TT genotype (OR = 1.59, 95% CI = 1.13-2.24). CONCLUSIONS These results highlighted the role of a genetic factor in ESCC and suggested that the PLCε1 rs2274223 SNP might be an effective genetic marker to assess the risk of ESCC in individuals with a UGIC family history from a region of high incidence in northern China.
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Affiliation(s)
- Rong-miao Zhou
- Department of Molecular Biology, The Fourth Affiliated Hospital of Hebei Medical University, Hebei Province, China
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Li XY, Guo YB, Su M, Cheng L, Lu ZH, Tian DP. Association of mitochondrial haplogroup D and risk of esophageal cancer in Taihang Mountain and Chaoshan areas in China. Mitochondrion 2011; 11:27-32. [PMID: 20601191 DOI: 10.1016/j.mito.2010.06.005] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2010] [Revised: 06/23/2010] [Accepted: 06/23/2010] [Indexed: 02/05/2023]
Abstract
Both the Taihang Mountain area in north-central China and Chaoshan area in the southeastern littoral of China are areas with high risk of esophageal cancer (EC). Our previous study confirmed that populations from the two areas might share similar matrilineal backgrounds and found that mitochondrial DNA (mtDNA) haplogroup D, especially subhaplogroups D4a and D5a, might be genetic background markers of EC in Chaoshan area. Here, to further determine whether D4a, D5a, and D might be susceptibility markers for EC in the two high-risk areas, we performed a case-control study with larger samples and analyzed the distributions of these three haplogroups in subjects (controls [n = 898] and patients [n = 768]) from the two areas. D4a haplogroup was significantly associated with increased risk of EC in Taihang Mountain subjects, especially women. D5 haplogroup was associated with EC at the general population level in the Taihang Mountain area and in subjects ≤ 60 years, especially women ≤ 60 years, in the Chaoshan area. D haplogroup was associated with EC only in subjects ≤ 60 years, especially men ≤ 60 years, in the Chaoshan area. D4a and D5 showing positive association with EC in the Taihang Mountain area became the predominant subhaplogroups of D in Chaoshan controls. In conclusion, D, D4a, and D5 haplogroups might be susceptibility markers for EC in the two high-risk areas in China, particularly D4a and D5 for the Taihang Mountain area and D and D5 for the Chaoshan area.
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Affiliation(s)
- Xiao-Yun Li
- Department of Pathology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province 515031, China
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Kong KL, Kwong DL, Fu L, Chan THM, Chen L, Liu H, Li Y, Zhu YH, Bi J, Qin YR, Law SYK, Guan XY. Characterization of a Candidate Tumor Suppressor Gene Uroplakin 1A in Esophageal Squamous Cell Carcinoma. Cancer Res 2010; 70:8832-41. [PMID: 20978196 DOI: 10.1158/0008-5472.can-10-0779] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Kar Lok Kong
- Department of Clinical Oncology and Center for Cancer Research and Department of Surgery, University of Hong Kong, Pokfulam, Hong Kong
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Wang LD, Zhou FY, Li XM, Sun LD, Song X, Jin Y, Li JM, Kong GQ, Qi H, Cui J, Zhang LQ, Yang JZ, Li JL, Li XC, Ren JL, Liu ZC, Gao WJ, Yuan L, Wei W, Zhang YR, Wang WP, Sheyhidin I, Li F, Chen BP, Ren SW, Liu B, Li D, Ku JW, Fan ZM, Zhou SL, Guo ZG, Zhao XK, Liu N, Ai YH, Shen FF, Cui WY, Song S, Guo T, Huang J, Yuan C, Huang J, Wu Y, Yue WB, Feng CW, Li HL, Wang Y, Tian JY, Lu Y, Yuan Y, Zhu WL, Liu M, Fu WJ, Yang X, Wang HJ, Han SL, Chen J, Han M, Wang HY, Zhang P, Li XM, Dong JC, Xing GL, Wang R, Guo M, Chang ZW, Liu HL, Guo L, Yuan ZQ, Liu H, Lu Q, Yang LQ, Zhu FG, Yang XF, Feng XS, Wang Z, Li Y, Gao SG, Qige Q, Bai LT, Yang WJ, Lei GY, Shen ZY, Chen LQ, Li EM, Xu LY, Wu ZY, Cao WK, Wang JP, Bao ZQ, Chen JL, Ding GC, Zhuang X, Zhou YF, Zheng HF, Zhang Z, Zuo XB, Dong ZM, Fan DM, He X, Wang J, Zhou Q, Zhang QX, Jiao XY, Lian SY, Ji AF, Lu XM, Wang JS, Chang FB, Lu CD, Chen ZG, Miao JJ, Fan ZL, Lin RB, Liu TJ, Wei JC, Kong QP, Lan Y, Fan YJ, Gao FS, Wang TY, Xie D, Chen SQ, Yang WC, Hong JY, Wang L, Qiu SL, Cai ZM, Zhang XJ. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nat Genet 2010; 42:759-63. [PMID: 20729853 DOI: 10.1038/ng.648] [Citation(s) in RCA: 332] [Impact Index Per Article: 22.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2010] [Accepted: 06/29/2010] [Indexed: 12/13/2022]
Abstract
We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
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Affiliation(s)
- Li-Dong Wang
- Cancer Research Center, Xinxiang Medical University, Xinxiang, Henan, China.
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Sun YL, Zhang JQ, Mao YH, Han LF, Ma YL, Lin ZW, Zhou LP, Wu M, Zhao XH. Epidemiological study of risk factors for esophageal cancer in Yangquan Area of Shanxi Province based on discordant sib pairs. Shijie Huaren Xiaohua Zazhi 2010; 18:1708-1713. [DOI: 10.11569/wcjd.v18.i16.1708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the main environmental risk factors for esophageal squamous cell carcinoma (ESCC) based on discordant sib pairs (DSPs) in a moderately high-incidence area, Yangquan City, Shanxi Province, and to provide theoretical evidence for developing effective control and prevention measures in this area.
METHODS: A 1:1 matched case-control study was carried out. One hundred and twenty-seven DSPs were recruited from the cancer registration and follow-up system of the local hospital. All ESCC cases and their matched unaffected sibs were subjected to a survey to obtain demographic information along with personal and family history, and lifestyle factors. The McNemar test was used for data analysis.
RESULTS: Compared with matched unaffected sibs, low family income (OR = 2.00, 95%CI: 1.14-3.52, P = 0.0143), hot food eating and drinking (OR = 2.56, 95%CI: 1.44-4.57, P = 0.0009) and heavy drinking (P = 0.0027) were risk factors for ESCC in the area. These factors play important roles in the development of ESCC, even in cases with a family history of ESCC, and the odds ratios (95%CI) were 2.18 (1.07-4.45), 5.00(1.91-13.06) and infinity, respectively.
CONCLUSION: Besides genetic factors, lack of nutrition, hot food eating and heavy drinking are main risk factors for ESCC in Yangquan City. Prevention and control of ESCC should be intervened at multiple levels, such as genetic factors and lifestyles.
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Liu M, Su M, Tian DP, Zhang GH, Yang HL, Gao YX. Heredity, diet and lifestyle as determining risk factors for the esophageal cancer on Nanao Island in Southern China. Fam Cancer 2010; 9:229-38. [PMID: 19916058 DOI: 10.1007/s10689-009-9300-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In this case-control study we evaluated contribution of environmental and genetic factors for risk of esophageal cancer (EC) by studying populations on Nanao Island (highest risk area for EC in China) and Shanwei (low risk region). Data on lifestyle, diet and family history were collected from the 166 newly diagnosed EC patients on Nanao between 2003 and 2004, from their 1450 first degree relatives and from controls on Nanao and Shanwei. Univariate and logistic regression analysis, family aggregation patterns, standardized incidence ratio (SIR), segregation ratio and heritability index were evaluated. The family cancer history was a significant risk factor for the two scenarios; Nanao cases versus Nanao controls, and Nanao controls versus Shanwei controls. Other risk factors included smoking, alcohol and fermented fish sauce. After adjusting for confounding variables, family history was independently associated with the occurrence of EC in Nanao cases versus Nanao controls. The incidence in the first degree relatives of Nanao cases was 0.86%, significantly higher than that of the public (0.12%) and SIR value was 1.44 in the first degree relatives of the 166 EC cases. The segregation ratio was 0.11 and the heritability index among first degree relatives was 40%. Our study indicates that there are steady pathogenic risk factors in the Nanao population's lifestyle but genetic factors also play an important role for EC onset.
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Affiliation(s)
- Min Liu
- Department of Oncology and Pathology, Shantou University Medical College, 22 Xinling Road, 515041, Shantou, Guangdong Province, China
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Guohong Z, Min S, DuenMei W, Songnian H, Min L, Jinsong L, Hongbin L, Feng Z, Dongping T, Heling Y, Zhicai L, Shiyong L, Quansheng G, Xiaoyun L, Yuxia G. Genetic heterogeneity of oesophageal cancer in high-incidence areas of southern and northern China. PLoS One 2010; 5:e9668. [PMID: 20300624 PMCID: PMC2837742 DOI: 10.1371/journal.pone.0009668] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 02/12/2010] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Oesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes. METHODS We conducted familial correlation, commingling, and complex segregation analyses of 224 families from the Chaoshan population and 403 families from the Taihang population using the FPMM program of S.A.G.E. version 5.3.0. A second analysis focused on specific families having large numbers of affected individuals or early onset of the disease. RESULTS For the general population, moderate sib-sib correlation was noticed for esophageal cancer. Additionally, brother-brother correlation was even higher. Commingling analyses indicated that a three-component distribution model best accounts for the variation in age of onset of oesophageal cancer, and that a multifactorial model provides the best fit to the general population data. An autosomal dominant mode and a dominant or recessive major gene with polygenic inheritance were found to be the best models of inherited susceptibility to oesophageal cancer in some large families. CONCLUSIONS The current results provide evidence for inherited susceptibility to oesophageal cancer in certain high-risk groups in China, and support efforts to identify the susceptibility genes.
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Affiliation(s)
- Zhang Guohong
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Su Min
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Wang DuenMei
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Hu Songnian
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Liu Min
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Li Jinsong
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Lin Hongbin
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Zhang Feng
- Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
| | - Tian Dongping
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Yang Heling
- Health Bureau of Nanao Island, Nanao, Guangdong Province, China
| | - Liu Zhicai
- Linzhou Tumor Hospital, Linzhou, Henan Province, China
| | - Lian Shiyong
- Linzhou Tumor Hospital, Linzhou, Henan Province, China
| | - Guo Quansheng
- Linzhou Tumor Hospital, Linzhou, Henan Province, China
| | - Li Xiaoyun
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
| | - Gao Yuxia
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China
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Hu SP, Zhou GB, Luan JA, Chen YP, Xiao DW, Deng YJ, Huang LQ, Cai KL. Polymorphisms of HLA-A and HLA-B genes in genetic susceptibility to esophageal carcinoma in Chaoshan Han Chinese. Dis Esophagus 2010; 23:46-52. [PMID: 19392852 DOI: 10.1111/j.1442-2050.2009.00965.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Esophageal carcinoma (EC) occurs at high rate in Chaoshan region of southern China. Human leukocyte antigen (HLA) polymorphism has been implicated in risk for various cancers. To investigate the impact of HLA-A and HLA-B polymorphisms on susceptibility to EC, a case-control study was conducted among 206 patients with esophageal squamous cell carcinoma and 524 controls from Chaoshan Han population. HLA-A and HLA-B polymorphisms were genotyped by polymerase chain reaction-sequence-specific primers. Genotypic association tests for dominant, recessive, and additive models, and haplotypic association were calculated using unconditional logistic regression. A*11 was identified in a recessive model as an only allele strongly associated with EC risk (odds ratios [OR]=2.10, 95% confidence interval [CI]=1.33-3.31) even after correction for multiple test. The haplotypes A*02-B*46 (OR=1.53, 95% CI=1.04-2.24) and A*11-B*51 (OR=2.29, 95% CI=1.20-4.40) showed association with increased risk for EC, whereas A*11-B*58 (OR=0.00, 95% CI=0.00-0.82) was associated with decreased risk, though the significance of these haplotypes was lost after correction. This is a first association study at genetic level identifying HLA-A and HLA-B-related variations in genetic susceptibility to EC among Chaoshan population. The variation pattern is likely to be EC-specific because it is different from that observed for nasopharyngeal carcinoma in the same study population and might, at least in part, explain the high rate of EC in this ethnic group.
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Affiliation(s)
- Sheng-Ping Hu
- Department of Thoracic Surgery, First Affiliated Hospital, and Center for Molecular Biology and Forensic Genetics Laboratory, Shantou University Medical College, Shantou, China.
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van der Zwaluw CS, Franke B, Engels RCME. Research Highlights. Pharmacogenomics 2009. [DOI: 10.2217/pgs.09.107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Carmen S van der Zwaluw
- Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands
| | - Barbara Franke
- Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands
| | - Rutger CME Engels
- Behavioural Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands
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A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway. Biochem J 2009; 422:363-72. [PMID: 19534726 DOI: 10.1042/bj20090465] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
S100A9 (S100 calcium-binding protein A9) is a calcium-binding protein of the S100 family, and its differential expression has been associated with acute and chronic inflammation and several human cancers. Our previous work showed that S100A9 was severely down-regulated in human ESCC (oesophageal squamous cell carcinoma). To further investigate the transcriptional regulation of S100A9, we analysed the S100A9 promoter region and found several putative p53BS (p53-binding sites). Luciferase reporter assays showed that constructs carrying the p53BS exhibited enhanced luciferase activity in response to wild-type p53 activation. Further study demonstrated that S100A9 mRNA and protein expression could be positively regulated in a p53-dependent manner and p53 could bind to p53BS on the S100A9 promoter. Overexpression of S100A9 could induce cellular apoptosis, and this was partly p53-dependent. Knockdown of S100A9 impaired the apoptosis induced by p53. Thus we conclude that a gene down-regulated in ESCC, S100A9, is a novel p53 transcriptional target, induces cellular apoptosis in a partly p53-dependent manner and mediates the p53 apoptosis pathway.
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Gao Y, Hu N, Han X, Giffen C, Ding T, Goldstein A, Taylor P. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China. BMC Cancer 2009; 9:269. [PMID: 19656375 PMCID: PMC2729777 DOI: 10.1186/1471-2407-9-269] [Citation(s) in RCA: 81] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2009] [Accepted: 08/05/2009] [Indexed: 02/08/2023] Open
Abstract
Background Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse. Methods 600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated. Results Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29). Conclusion These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.
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Affiliation(s)
- Ying Gao
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA.
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Sun L, König IR, Homann N. Manganese superoxide dismutase (MnSOD) polymorphism, alcohol, cigarette smoking and risk of oesophageal cancer. Alcohol Alcohol 2009; 44:353-7. [PMID: 19451660 DOI: 10.1093/alcalc/agp025] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
AIMS Alcohol, tobacco smoke and Barrett's oesophagus as a consequence of gastro-oesophageal reflux are the main risk factors in oesophageal carcinogenesis. All risk factors may induce oxidative stress. Manganese superoxide dismutase (MnSOD) is one important repair enzyme for reactive oxidative stress (ROS)-induced damage. MnSOD polymorphisms in the -9 position of the signal sequence of the protein may lead to critical enzyme deficiency. The aim of the present study was to investigate the role of polymorphisms of MnSOD in patients with oesophageal cancer [n = 170, 61 patients with adenocarcinoma (AC), 109 patients with squamous cell carcinoma (SCC)] compared to heavy drinkers (n = 160) and healthy blood donors (n = 400). METHODS Genotyping was performed by PCR-RFLP analysis using genomic DNA extracted from whole blood. RESULTS The Ala/Ala genotype was 27.7% in cancer patients (29.5% AC, 26.6% SCC), 23.1% in patients with heavy alcohol abuse and 12.5% in the group of healthy blood donors. These results were not statistically significant after multivariate analysis controlling for age, sex, alcohol, cigarettes and interactions (odds ratio 0.92, 95% confidence interval = 0.63-1.36, for cancer patients versus heavy drinkers; odds ratio 1.02, 95% confidence interval = 0.51-2.03, for cancer patients versus blood donors; analysis by logistic regression). Subjects with an Ala/Ala genotype (81.3 g/day) had a significantly higher alcohol intake than those with Val/Ala (63.9 g/day) or Val/Val (53.8 g/day) genotype (P < 0.00001 by the Kruskal-Wallis test). CONCLUSIONS MnSOD polymorphisms play no role in the genetic predisposition to oesophageal cancer. However, our data suggest a complex gene-to-phenotype interaction between the MnSOD genotype and alcohol misuse.
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Affiliation(s)
- L Sun
- Department of Medicine I, University Hospital of Schleswig Holstein, Campus Lübeck, Germany
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Qin JM, Yang L, Chen B, Wang XM, Li F, Liao PH, He L. Interaction of methylenetetrahydrofolate reductase C677T, cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population. World J Gastroenterol 2008; 14:6986-92. [PMID: 19058336 PMCID: PMC2773864 DOI: 10.3748/wjg.14.6986] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CYP4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China.
METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 population- or hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis.
RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502E1C1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502E1C1/C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone.
CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.
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Jain M, Kumar S, Ghoshal UC, Mittal B. Association of ECRG2 TCA short tandem repeat polymorphism with the risk of oesophageal cancer in a North Indian population. Clin Exp Med 2008; 8:73-8. [PMID: 18618216 DOI: 10.1007/s10238-008-0160-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2007] [Accepted: 01/28/2008] [Indexed: 10/21/2022]
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Abstract
Chronic mucocutaneous candidiasis (CMC) is often accompanied by endocrine or inflammatory disorders. The association of CMC with squamous cell carcinoma of the oral cavity or oesophagus have been described in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). We describe three cases of CMC and oesophageal cancer without the APECED syndrome. The first case refers to a 41-year-old man with Candida paronychia and oral infection and selective IgA deficiency since childhood, who later developed an oesophageal cancer. The second case is a 30-year-old man who presented CMC features at the age of 2 together with selective IgA deficiency. Later on he was diagnosed with an oesophageal squamous cell carcinoma. His mother, the third case reported, had oral thrush since childhood and at the age of 29 she presented with an oesophageal squamous cell carcinoma. The three patients reported died due to oesophageal cancer. This is the first case report describing the development of oesophageal cancer in patients with CMC without the APECED syndrome. Patients with CMC need close follow-up with good oral hygiene and aggressive treatment of oral and oesophageal candidiasis. Routine endoscopic screening for patients with CMC that develop symptoms of oesophageal candidiasis and for patients with CMC with a family history of oesophageal cancer is suggested. Avoidance of additional risk factors for oral and oesophageal cancer like cigarette smoking and excessive alcohol consumption are also warranted.
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Affiliation(s)
- Daniela D Rosa
- Paterson Institute for Cancer Research, Cancer Research UK, Manchester
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Shen Y, Xu Q, Han Z, Liu H, Zhou GB. Analysis of phenotype-genotype connection: the story of dissecting disease pathogenesis in genomic era in China, and beyond. Philos Trans R Soc Lond B Biol Sci 2007; 362:1043-61. [PMID: 17327209 PMCID: PMC2435570 DOI: 10.1098/rstb.2007.2033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
DNA is the ultimate depository of biological complexity. Thus, in order to understand life and gain insights into disease pathogenesis, genetic information embedded in the sequence of DNA base pairs comprising chromosomes should be deciphered. The stories of investigating the association between phenotype and genotype in China and other countries further demonstrate that genomics can serve as a probe for disease biology. We now know that in Mendelian disorders, one gene is not only a dictator of one phenotype but also a dictator of two or more distinct disorders. Dissecting genetic abnormalities of complex diseases, including diabetes, hypertension, mental diseases, coronary heart disease and cancer, may unravel the complicated networks and crosstalks, and help to simplify the complexity of the disease. The transcriptome and proteomic analysis for medicine not only deepen our understanding of disease pathogenesis, but also provide novel diagnostic and therapeutic strategies. Taken together, genomic research offers a new opportunity for determining how diseases occur, by taking advantage of experiments of nature and a growing array of sophisticated research tools to identify the molecular abnormalities underlying disease processes. We should be ready for the advent of genomic medicine, and put the genome into the doctors' bag, so that we can help patients to conquer diseases.
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Affiliation(s)
- Yan Shen
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences100005 Beijing, People's Republic of China
- Chinese National Human Genome Center at Beijing100176 Beijing, People's Republic of China
- Authors for correspondence () ()
| | - Qi Xu
- State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College & Chinese Academy of Medical Sciences100005 Beijing, People's Republic of China
| | - Zeguang Han
- Chinese National Human Genome Center at Shanghai201203 Shanghai, People's Republic of China
| | - Han Liu
- State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology200025 Shanghai, People's Republic of China
| | - Guang-Biao Zhou
- Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences510663 Guangzhou, People's Republic of China
- Authors for correspondence () ()
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Chen AG, Yu ZC, Yu XF, Cao WF, Ding F, Liu ZH. Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma. World J Gastroenterol 2006; 12:7859-63. [PMID: 17203534 PMCID: PMC4087556 DOI: 10.3748/wjg.v12.i48.7859] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the expression pattern of Ets-like protein 1 (Elk-1) in human esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with clinicopathologic parameters.
METHODS: The expression of Elk-1 in fresh esophageal cancer tissues and their corresponding normal mucosae was detected immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 13.0.
RESULTS: Expression level of transcription factor Elk-1 increased in 78.5% (84/107) ESCC tissues compared with their matched normal esophageal epithelium. However, the expression of Elk-1 did not show any obvious correlation with degree of differentiation of esophageal carcinoma (in well-differentiated, moderately-differentiated and poorly-differentiated tumors, the increased expression was 7/8, 60/74, and 19/25, respectively, P > 0.05). Moreover, no obvious correlation was found with lymph node metastasis and depth of invasion.
CONCLUSION: Increased expression of transcription factor Elk-1 may play an important role in esophageal carcinogenesis.
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Affiliation(s)
- An-Guo Chen
- Department of Thoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
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Liu W, Yu ZC, Cao WF, Ding F, Liu ZH. Functional studies of a novel oncogene TGM3 in human esophageal squamous cell carcinoma. World J Gastroenterol 2006; 12:3929-32. [PMID: 16804985 PMCID: PMC4087948 DOI: 10.3748/wjg.v12.i24.3929] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the role of transglutaminase 3 (TGM3) gene in human esophageal squamous cell carcinoma (ESCC), and analyze its relationship with clinicopathological parameters.
METHODS: Gene expression of TGM3 in fresh esophageal cancer tissues and their corresponding normal mucosas was detected immunohistochemically(IHC) by means of tissue microarray(TMA). Its correlation with clinical characteristics was evaluated and analyzed by univariate analysis. All statistical analyses were performed by SPSS version 10.0.
RESULTS: Expression rate of TGM3 was reduced to 81.8% in ESCC. Expression of TGM3 was significantly inversely correlated with histological grade of esophageal carcinoma (in grade I, II and III tumors, the reduced expression was 4/7, 57/71, and 20/21, respectively, P < 0.05), whereas it had no obvious correlations with lymph node metastasis and depth of invasion.
CONCLUSION: Reduced expression of TGM3 may play an important role in esophageal carcinogenesis.
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Affiliation(s)
- Wei Liu
- Department of Thoracic Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China
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Zhang L, Ding F, Cao W, Liu Z, Liu W, Yu Z, Wu Y, Li W, Li Y, Liu Z. Stomatin-like Protein 2 Is Overexpressed in Cancer and Involved in Regulating Cell Growth and Cell Adhesion in Human Esophageal Squamous Cell Carcinoma. Clin Cancer Res 2006; 12:1639-46. [PMID: 16533792 DOI: 10.1158/1078-0432.ccr-05-1858] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It has been implicated in interaction with erythrocyte cytoskeleton and presumably other integral membrane proteins, but not directly with the membrane bilayer. We show here the involvement of SLP-2 in human esophageal squamous cell carcinoma (ESCC), lung cancer, laryngeal cancer, and endometrial adenocarcinoma and the effects of SLP-2 on ESCC cells. EXPERIMENTAL DESIGN Previous work of cDNA microarray in our laboratory revealed that SLP-2 was significantly up-regulated in ESCC. The expression of SLP-2 was further evaluated in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma by semiquantitative reverse transcription-PCR, Western blot, and immunohistochemistry. Mutation detection of SLP-2 exons was done by PCR and automated sequencing. Antisense SLP-2 eukaryotic expression plasmids were constructed and transfected into human ESCC cell line KYSE450. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, clonogenecity assay, flow cytometry assay, nude mice tumorigenetic assay, and cell attachment assay were done to investigate the roles of SLP-2 gene. RESULTS All tumor types we tested showed overexpression of SLP-2 compared with their normal counterparts (P < or = 0.05). Moreover, immunohistochemistry analysis of mild dysplasia, severe dysplasia, and ESCC showed that overexpression of SLP-2 occurred in premalignant lesions. Mutation analysis indicated that no mutation was found in SLP-2 exons. KYSE450 cells transfected with antisense SLP-2 showed decreased cell growth, proliferation, tumorigenecity, and cell adhesion. CONCLUSIONS SLP-2 was first identified as a novel cancer-related gene overexpressed in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma. Decreased cell growth, cell adhesion, and tumorigenesis in the antisense transfectants revealed that SLP-2 may be important in tumorigenesis.
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MESH Headings
- Adenocarcinoma/genetics
- Adenocarcinoma/metabolism
- Adenocarcinoma/pathology
- Animals
- Blood Proteins/genetics
- Blood Proteins/immunology
- Blood Proteins/pharmacology
- Blotting, Western
- Carcinoma, Squamous Cell/genetics
- Carcinoma, Squamous Cell/metabolism
- Carcinoma, Squamous Cell/pathology
- Cell Adhesion
- Cell Proliferation
- DNA, Antisense/pharmacology
- Endometrial Neoplasms/genetics
- Endometrial Neoplasms/metabolism
- Endometrial Neoplasms/pathology
- Esophageal Neoplasms/genetics
- Esophageal Neoplasms/metabolism
- Esophageal Neoplasms/pathology
- Female
- Flow Cytometry
- Gene Expression Regulation, Neoplastic
- Humans
- Laryngeal Neoplasms/genetics
- Laryngeal Neoplasms/metabolism
- Laryngeal Neoplasms/pathology
- Lung Neoplasms/genetics
- Lung Neoplasms/metabolism
- Lung Neoplasms/pathology
- Male
- Membrane Proteins/genetics
- Membrane Proteins/immunology
- Membrane Proteins/pharmacology
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Mutation
- RNA, Neoplasm/genetics
- RNA, Neoplasm/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Cells, Cultured
- Tumor Stem Cell Assay
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Affiliation(s)
- Liyong Zhang
- National Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Jia WH, Collins A, Zeng YX, Feng BJ, Yu XJ, Huang LX, Feng QS, Huang P, Yao MH, Shugart YY. Complex segregation analysis of nasopharyngeal carcinoma in Guangdong, China: evidence for a multifactorial mode of inheritance (complex segregation analysis of NPC in China). Eur J Hum Genet 2005; 13:248-52. [PMID: 15483644 DOI: 10.1038/sj.ejhg.5201305] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The striking geographical and ethnic distribution of nasopharyngeal carcinoma (NPC) suggests the involvement of genetic and environmental factors in NPC development. The purpose of this study is to investigate the fit of single gene, polygenic and multifactorial models to the observed pattern of transmission of NPC in a hospital-based family history study conducted by the Cancer Center of Sun Yat-Sen University (CCSYU) in Guangzhou, China. Complex segregation analysis of a total of 1903 Cantonese pedigrees ascertained at CCSYU was conducted using a unified mixed model after the pedigrees were partitioned into 3737 nuclear families. The mixed model assumes that a phenotype is influenced by the additive and independent effect of a major gene, together with multifactorial components (genetic and environmental) and a random environmental effect. The current results do not provide evidence for a major gene and the observed data are best explained by a multifactorial mode of inheritance for NPC.
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Affiliation(s)
- Wei-Hua Jia
- Department of Experimental Research, Cancer Center, Sun Yat-sen University, GuangZhou 510060, China
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Guo W, Wang N, Wang YM, Li Y, Wen DG, Chen ZF, He YT, Zhang JH. Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China. World J Gastroenterol 2005; 11:858-62. [PMID: 15682481 PMCID: PMC4250597 DOI: 10.3748/wjg.v11.i6.858] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China.
METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203 ESCC and 152 GCA) and 443 healthy controls.
RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42 and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively). Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10, 95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%, 39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6% and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P>0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95% CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46) in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes.
CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.
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Affiliation(s)
- Wei Guo
- Hebei Cancer Institute, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei Province, China
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Zhang LY, Wang T, Ding F, Liu ZM, Liu ZH, Li YD. Differential expression and bioinformatics analysis of SLP-2 gene in esophageal squamous cell carcinoma. Shijie Huaren Xiaohua Zazhi 2004; 12:1517-1521. [DOI: 10.11569/wcjd.v12.i7.1517] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: One of the differentially expressed genes, SLP-2 (stomatin-like protein 2, SLP-2), was obtained from esophageal squamous cell carcinoma (ESCC) patient-matched tissues using cDNA microarrays, which was overexpressed in ESCC tissues compared with their normal counterparts. This study was to confirm overexpression of SLP-2 in ESCC, to construct tissue expression pattern of SLP-2 in different embryonic tissues and to carry out bioinformatics analysis.
METHODS: Overexpression of SLP-2 in esophageal squamous cell carcinoma was confirmed by RT-PCR and Northern blot. Tissue expression pattern was constructed by RT-PCR. And the biological property was analyzed by bioinformatic softwares.
RESULTS: RT-PCR and Northern blot showed that SLP-2 was overexpressed in ESCC tissues and distributed in different embryonic tissues. Relatedness between members of the stomatin superfamily was compared using CLUSTAL procedure. Simple Modular Architecture Research Tool (SMART) software predicted that it possessed a PHB domain (prohibitin homologue) and a coiled coil.
CONCLUSION: cDNA microarray is a powerful tool for screening differentially expressed genes. SLP-2 is overex-pressed in ESCC tissues and expressed in different embryonic tissues. The biological property is analyzed by bioinformatic softwares. Our study lays a good foundation for elucidation the molecular mechanism of initiation and progression of ESCC.
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Kong JP, Ding F, Zhou CN, Wang XQ, Miao XP, Wu M, Liu ZH. Loss of myeloid-related proteins 8 and myeloid-related proteins 14 expression in human esophageal squamous cell carcinoma correlates with poor differentiation. World J Gastroenterol 2004; 10:1093-7. [PMID: 15069705 PMCID: PMC4656340 DOI: 10.3748/wjg.v10.i8.1093] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study the expression of myeloid-related proteins (MRP)8 and myeloid-related proteins(MRP)14 in human esophageal squamous cell carcinoma and to investigate if there was any correlation between MRP8 and MRP14 expression level and histopathological grade in these tumors.
METHODS: In this study, 65 cases of advanced esophageal squamous cell carcinoma were assessed for MRP8 and MRP14 expression using immunohistochemistry. Statistical analysis was performed for the comparison of MRP8 and MRP14 expression in normal and tumor tissues, and their relationship with clinicopathological features.
RESULTS: Reduced or absent expression of MRP8 and MRP14 was observed in esophageal squamous cell carcinoma, with a significant difference between tumor tissues and normal tissues (P < 0.01 and P < 0.01 for MRP8 and MRP14, respectively). Poorly differentiated tumors presented a greater decrease than well and moderately differentiated tumors, with a correlation between their protein level and histopathological grading (P < 0.001 and P < 0.001, respectively). However, no significant association was found between MRP8 and MRP14 expression and age or gender (P > 0.05).
CONCLUSION: These findings suggest that the decreased expression of MRP8 and MRP14 might play an important role in the pathogenesis of human esophageal squamous cell carcinoma, being particularly associated with poor differentiation of tumor cells.
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Affiliation(s)
- Jian-Ping Kong
- National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Wang AH, Sun CS, Li LS, Huang JY, Chen QS, Xu DZ. Genetic susceptibility and environmental factors of esophageal cancer in Xi’an. World J Gastroenterol 2004; 10:940-4. [PMID: 15052670 PMCID: PMC4717108 DOI: 10.3748/wjg.v10.i7.940] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To analyse the role of genetic susceptibility and environmental factors in the process of esophageal cancer (EC) formation in Xi’an, China.
METHODS: A hospital based case-control study, combined with molecular epidemiological method, was carried out. A total of 127 EC cases and 101 controls were interviewed with questionnaires containing demographic items, habit of tobacco smoking, alcohol drinking, and family history of EC. Polymorphism of CYP1A1 and GSTM1 of 127 EC cases and 101 controls were detected by PCR method. The interactions between genetic susceptibility and environmental factors were also discussed.
RESULTS: Tobacco smoking, alcohol drinking and a family history of EC were risk factors for EC with an OR of 2.04 (95%CI 1.15-3.60), 3.45(95%CI 1.74-6.91), 3.14 (95%CI 1.28-7.94), respectively. Individuals carrying CYP1A1 Val/Val genotype compared to those with CYP1A1 Ile/Ile genotype had an increased risk for EC (OR 3.35, 95%CI 1.49-7.61). GSTM1 deletion genotype was a risk factor for EC (OR1.81, 95%CI 1.03-3.18). Gene-environment interaction analysis showed that CYP1A1 Val/Val genotype, GSTM1 deletion genotype had synergetic interactions with tobacco smoking, alcohol drinking and family history of EC.
CONCLUSION: Tobacco smoking, alcohol drinking and a family history of EC are risk factors for EC. CYP1A1 Val/Val and GSTM1 deletion genotypes are genetic susceptibility biomarkers for EC. There are synergic interactions between genetic susceptibility and environmental factors.
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Affiliation(s)
- An-Hui Wang
- Department of Epidemiology, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an 710033, Shanxi Province, China.
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Luo A, Kong J, Hu G, Liew CC, Xiong M, Wang X, Ji J, Wang T, Zhi H, Wu M, Liu Z. Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene 2004; 23:1291-9. [PMID: 14647409 DOI: 10.1038/sj.onc.1207218] [Citation(s) in RCA: 162] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.
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Affiliation(s)
- Aiping Luo
- National Lab of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, P.R. China
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50
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Zhi H, Zhang J, Hu G, Lu J, Wang X, Zhou C, Wu M, Liu Z. The deregulation of arachidonic acid metabolism-related genes in human esophageal squamous cell carcinoma. Int J Cancer 2003; 106:327-33. [PMID: 12845669 DOI: 10.1002/ijc.11225] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is 1 of the most common cancers worldwide. In our study, cDNA microarray comprising 14,803 genes was employed to identify gene-specific expression profile in 6 paired samples of ESCC. Nine genes identified were commonly upregulated and 36 downregulated in tumors, as compared to normal esophageal squamous epithelia. Among these genes, we found that 9 of the altered expression genes were related to arachidonic acid (AA) metabolism, such as annexin-I, annexin-II, S100A8, S100A10, S100P, glutathione peroxidase-3, phosphatidylcholine transfer protein, aldo-keto reductase family 1 and cyclooxygenase-2 (COX-2). To gain insights into the regulation of the AA metabolism pathway involved in the carcinogenesis of ESCC, we investigated the expression of 8 genes related to the AA metabolism by semiquantitative reverse transcript (RT)-PCR and/or Western blot and immunohistochemistry. These genes include annexin-I, annexin-II, COX-2, cyclooxygenase-1 (COX-1) and cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP) and 12-lipoxygenase (12-LOX) (not included in the array data). The expression level of annexin-I, annexin-II was downregulated in esophageal cancer, whereas cPLA(2), FLAP, COX-2, 5-LOX and 12-LOX were upregulated. These data suggested that AA metabolism pathway and its altered expression may contribute to esophageal squamous cell carcinogenesis.
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Affiliation(s)
- Huiying Zhi
- National Lab of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100 021, People's Republic of China
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