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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (01) : 1 -9. doi: 10.3877/cma.j.issn.1674-0785.2021.01.001

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食管鳞癌精准防治基础研究概述
柯杨1,()   
  1. 1. 100142 北京,北京大学肿瘤医院 北京肿瘤医院暨北京市肿瘤防治研究所遗传学研究室 恶性肿瘤发病机制及转化研究教育部重点实验室
  • 收稿日期:2020-10-27 出版日期:2021-01-15
  • 通信作者: 柯杨

Overview of basic research on precision prevention and treatment of esophageal squamous cell carcinoma

Yang Ke1,()   

  1. 1. Peking University Cancer Hospital, Genetics Laboratory, Beijing Cancer Hospital & Beijing Cancer Prevention and Control Institute, The Ministry of Education (MOE) Key Laboratory of Carcinogenesis and Translational Research, Beijing 100142, China
  • Received:2020-10-27 Published:2021-01-15
  • Corresponding author: Yang Ke
引用本文:

柯杨. 食管鳞癌精准防治基础研究概述[J]. 中华临床医师杂志(电子版), 2021, 15(01): 1-9.

Yang Ke. Overview of basic research on precision prevention and treatment of esophageal squamous cell carcinoma[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(01): 1-9.

本文回顾了我国科学家在食管鳞癌病因学、分子机制研究及早诊早治方面的努力和成效,提出:(1)食管鳞癌作为典型复杂因果疾病,保护食管免受各种物理化学损伤至关重要;(2)有必要在各种组学研究基础上,采用高规格前瞻性人群研究设计,整合已有结果开展系统分析,深入挖掘潜在干预靶点;(3)在尚未发现高归因风险致病因素的情况下,大规模筛查需随机对照研究对其效果及卫生经济学价值加以评估,同时需进一步推动现有筛查模式不断向精准化与个体化方向发展。

This paper reviews the efforts and achievements of Chinese scientists in studying the pathogenesis, molecular mechanism, and early diagnosis and treatment of esophageal squamous cell carcinoma (ESCC) based on our work. It is suggested that: (1) ESCC is a typical multifactorial disease, and it is very important to protect the esophagus from various physical and chemical injuries to prevent the development of this malignancy; (2) based on a variety of omics studies, it is necessary to adopt a high-quality prospective population study design, integrate existing results to carry out systematic analysis, and explore potential intervention targets in depth; and (3) in the absence of high attributable risk factors, large-scale screening needs to be evaluated in randomized controlled studies to evaluate its effects and health economic value, and at the same time, existing screening models need to be further improved with regard to precision and individualization.

表1 来自中国人群的ESCC GWAS研究鉴定出的SNP位点信息
作者 年份 期刊 技术方法 病例/对照 易感位点 OR值(95%CI)
Abnet Christian C 2010 Nature Genetics GWAS 2115/3302 10q23(PLCE1 rs2274223) 1.34(1.22~1.48)
Wang Lidong 2010 Nature Genetics GWAS 9053/13 283(GWAS:1077/1733;Validation:7976/11 550) 10q23(PLCE1 rs2274223) 1.43(1.37~1.49)
Wu Chen 2011 Nature Genetics GWAS 8307/8209(GWAS:2031/2044;Validation:6276/6165) 5q11(PDE4D rs10052657) 0.67(0.62~0.73)
21q22(RUNX1 rs2014300) 0.70(0.65~0.75)
6p21(rs10484761) 1.33(1.23~1.45)
10q23(PLCE1 rs2274223) 1.34(1.26~1.42)
12q24(rs11066280) 1.30(1.22~1.38)
12q24(C12orf51 rs2074356) 1.56(1.45~1.68)
12q24(ACAD10 rs11066015) 1.38(1.29~1.48)
Abnet Christian C 2012 Human Molecular Genetics Meta-analysis of two GWAS(Abnet Christian C 2010 and Wang Lidong 2010) 2961/3400(2024/2708;937/692) 2q33(CASP8 rs10931936) 1.27(1.17~1.38)
2q33(ALS2CR12 rs13016963) 1.29(1.19~1.40)
2q33(ALS2CR12 rs9288318) 1.28(1.18~1.39)
2q33(ALS2CR12 rs10201587) 1.29(1.19~1.40)
2q33(TRAK2 rs7578456) 1.27(1.17~1.38)
Wu Chen 2012 Nature Genetics GWAS from Wu Chen(2011) 10123/10664(GWAS:2031/2044;Validation 8092/8620) 2q22(IGFBP2 rs9288520) 1.09(1.02~1.16)
13q33(SLC10A2 rs17450420) 1.34(1.16~1.54)
3q27(ST6GAL1 rs2239612) 1.21(1.15~1.27)
22q12(XBP1 rs2239815) 1.18(1.13~1.23)
22q12(CHEK2 rs4822983) 1.27(1.21~1.34)
22q12(CHEK2 rs1033667) 1.25(1.19~1.30)
16q12.1(HEATR3 rs4785204) 1.24(1.18~1.29)
16q12.1(HEATR3 rs7206735) 1.20(1.15~1.26)
4q23(ADH1B rs1042026) 1.35(1.29~1.41)
Wu Chen 2014 Nature Genetics Joint analysis of three GWAS(Abnet Christian C 2010,Wang Lidong 2010 and Wu Chen 2011) 14991/15845(GWAS:5337/5787;Validation:9654/10058) 5q31.2(TMEM173 rs7447927) 0.85(0.82~0.88)
17p13.1(ATP1B2 rs1642764) 0.88(0.85~0.91)
6p21.32(HLA class II rs35597309) 1.19(1.12~1.27)
表2 基于全基因组测序和全外显子测序开展的食管鳞状细胞癌研究汇总
1
郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析 [J]. 中华肿瘤杂志, 2019, 41(1): 19-28.
2
Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma [J]. Gastroenterology, 2018, 154(2): 360-373.
3
He Z, Liu Z, Liu M, et al. Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomised controlled trial [J]. Gut, 2019, 68(2): 198-206.
4
He Z, Zhao Y, Guo C, et al. Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey [J]. Br J Cancer, 2010, 103(7): 1085-1088.
5
Tran GD, Sun XD, Abnet CC, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China [J]. Int J Cancer, 2005, 113(3): 456-463.
6
Li JY, Chen ZJ, Ershow AG, et al. A case-control study of esophageal cancer in Linxian, People's Republic of China [J]. Natl Cancer Inst Monogr, 1985, 69: 5-7.
7
Li JY, Taylor PR, Li B, et al. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia [J]. J Natl Cancer Inst, 1993, 85(18): 1492-1498.
8
Wang SM, Abnet CC, Qiao YL. What have we learned from Linxian esophageal cancer etiological studies? [J]. Thorac Cancer, 2019, 10(5): 1036-1042.
9
Wei WQ, Abnet CC, Lu N, et al. Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China [J]. Gut, 2005, 54(6): 759-763.
10
Sheikh M, Poustchi H, Pourshams A, et al. Individual and combined effects of environmental risk factors for esophageal cancer based on results from the Golestan cohort study [J]. Gastroenterology, 2019, 156(5): 1416-1427.
11
Chen W, Li H, Ren J, et al. Selection of high-risk individuals for esophageal cancer screening: A prediction model of esophageal squamous cell carcinoma based on a multicenter screening cohort in rural China [J]. Int J Cancer, 2020, 148(2): 329-339.
12
Liu M, Liu Z, Cai H, et al. A model to identify individuals at high risk for esophageal squamous cell carcinoma and precancerous lesions in regions of high prevalence in China [J]. Clin Gastroenterol Hepatol, 2017, 15(10): 1538-1546. e7.
13
Yu C, Tang H, Guo Y, et al. Hot tea consumption and its interactions with alcohol and tobacco use on the risk for esophageal cancer: a population-based cohort study [J]. Ann Intern Med, 2018, 168(7): 489-497.
14
Tuyns AJ, Masse G. Cancer of the oesophagus in Brittany: an incidence study in Ille-et-Vilaine [J]. Int J Epidemiol, 1975, 4(1): 55-59.
15
Engel LS, Chow WH, Vaughan TL, et al. Population attributable risks of esophageal and gastric cancers [J]. J Natl Cancer Inst, 2003, 95(18): 1404-1413.
16
Arnold M, Soerjomataram I, Ferlay J, et al. Global incidence of oesophageal cancer by histological subtype in 2012 [J]. Gut, 2015, 64(3): 381-387.
17
GBD 2017 Oesophageal Cancer Collaborators. The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J]. Lancet Gastroenterol Hepatol, 2020, 5(6): 582-597.
18
Di Pilato V, Freschi G, Ringressi MN, et al. The esophageal microbiota in health and disease [J]. Ann N Y Acad Sci, 2016, 1381(1): 21-33.
19
Yu G, Gail MH, Shi J, et al. Association between upper digestive tract microbiota and cancer-predisposing states in the esophagus and stomach [J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(5): 735-741.
20
Vogtmann E, Flores R, Yu G, et al. Association between tobacco use and the upper gastrointestinal microbiome among Chinese men [J]. Cancer Causes Control, 2015, 26(4): 581-588.
21
Chen X, Winckler B, Lu M, et al. Oral microbiota and risk for esophageal squamous cell carcinoma in a high-risk area of China [J]. PLoS One, 2015, 10(12): e0143603.
22
Nasrollahzadeh D, Malekzadeh R, Ploner A, et al. Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia [J]. Sci Rep, 2015, 5: 8820.
23
Yamamura K, Izumi D, Kandimalla R, et al. Intratumoral fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma [J]. Clin Cancer Res, 2019, 25(20): 6170-6179.
24
Shao D, Vogtmann E, Liu A, et al. Microbial characterization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-risk region of China [J]. Cancer, 2019, 125(22): 3993-4002.
25
Robert LG, Dimaio D. The papillomaviruses [M]. New York: Springer, 2007.
26
Liu F, Guo F, Zhou Y, et al. The anyang esophageal cancer cohort study: study design, implementation of fieldwork, and use of computer-aided survey system [J]. PLoS One, 2012, 7(2): e31602.
27
Liu M, Liu F, Pan Y, et al. Viral load in the natural history of human papillomavirus infection among men in rural China: a population-based prospective study [J]. Clin Infect Dis, 2018, 67(12): 1861-1867.
28
Hang D, Liu F, Liu M, et al. Oral human papillomavirus infection and its risk factors among 5,410 healthy adults in China, 2009-2011 [J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(10): 2101-2110.
29
Liu M, He Z, Zhang C, et al. Prevalence, incidence, clearance, and associated factors of genital human papillomavirus infection among men: a population-based cohort study in rural China [J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(12): 2857-2865.
30
Deng Q, Li J, Pan Y, et al. Prevalence and associated risk factors of human papillomavirus in healthy skin specimens collected from rural Anyang, China, 2006-2008 [J]. J Invest Dermatol, 2016, 136(6): 1191-1198.
31
Abnet CC, Freedman ND, Hu N, et al. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma [J]. Nat Genet, 2010, 42(9): 764-767.
32
Wang LD, Zhou FY, Li XM, et al. Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54 [J]. Nat Genet, 2010, 42(9): 759-763.
33
Wu C, Hu Z, He Z, et al. Genome-wide association study identifies three new susceptibility loci for esophageal squamous-cell carcinoma in Chinese populations [J]. Nat Genet, 2011, 43(7): 679-684.
34
Abnet CC, Wang Z, Song X, et al. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies [J]. Hum Mol Genet, 2012, 21(9): 2132-2141.
35
Wu C, Kraft P, Zhai K, et al. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions [J]. Nat Genet, 2012, 44(10): 1090-1097.
36
Wu C, Wang Z, Song X, et al. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations [J]. Nat Genet, 2014, 46(9): 1001-1006.
37
Dai J, Lv J, Zhu M, et al. Identification of risk loci and a polygenic risk score for lung cancer: a large-scale prospective cohort study in Chinese populations [J]. Lancet Respir Med, 2019, 7(10): 881-891.
38
Jin G, Lv J, Yang M, et al. Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study [J]. Lancet Oncol, 2020, 21(10): 1378-1386.
39
Agrawal N, Jiao Y, Bettegowda C, et al. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma [J]. Cancer Discov, 2012, 2(10): 899-905.
40
Gao YB, Chen ZL, Li JG, et al. Genetic landscape of esophageal squamous cell carcinoma [J]. Nat Genet, 2014, 46(10): 1097-1102.
41
Lin DC, Hao JJ, Nagata Y, et al. Genomic and molecular characterization of esophageal squamous cell carcinoma [J]. Nat Genet, 2014, 46(5): 467-473.
42
Song Y, Li L, Ou Y, et al. Identification of genomic alterations in oesophageal squamous cell cancer [J]. Nature, 2014, 509(7498): 91-95.
43
Wang Q, Bai J, Abliz A, et al. An old story retold: loss of G1 control defines a distinct genomic subtype of esophageal squamous cell carcinoma [J]. Genomics, Proteomics Bioinformatics, 2015, 13(4): 258-270.
44
Zhang L, Zhou Y, Cheng C, et al. Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma [J]. Am J Hum Genet, 2015, 96(4): 597-611.
45
Hao JJ, Lin DC, Dinh HQ, et al. Spatial intratumoral heterogeneity and temporal clonal evolution in esophageal squamous cell carcinoma [J]. Nat Genet, 2016, 48(12): 1500-1507.
46
Sawada G, Niida A, Uchi R, et al. Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population [J]. Gastroenterology, 2016, 150(5): 1171-1182.
47
Qin HD, Liao XY, Chen YB, et al. Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis [J]. Am J Hum Genet, 2016, 98(4): 709-727.
48
Hu N, Kadota M, Liu H, et al. Genomic landscape of somatic alterations in esophageal squamous cell carcinoma and gastric cancer [J]. Cancer Res, 2016, 76(7): 1714-1723.
49
Cancer Genome Atlas Research N, Analysis Working Group: Asan U, Agency BCC, et al. Integrated genomic characterization of oesophageal carcinoma [J]. Nature, 2017, 541(7636): 169-175.
50
Liu X, Zhang M, Ying S, et al. Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma [J]. Gastroenterology, 2017, 153(1): 166-177.
51
Chen XX, Zhong Q, Liu Y, et al. Genomic comparison of esophageal squamous cell carcinoma and its precursor lesions by multi-region whole-exome sequencing [J]. Nat Commun, 2017, 8(1): 524.
52
Chang J, Tan W, Ling Z, et al. Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations [J]. Nat Commun, 2017, 8(1): 15290.
53
Yuan W, Liu Z, Wang Y, et al. Clonal evolution of esophageal squamous cell carcinoma from normal mucosa to primary tumor and metastases [J]. Carcinogenesis, 2019, 40(12): 1445-1451.
54
Park S, Joung JG, Min YW, et al. Paired whole exome and transcriptome analyses for the immunogenomic changes during concurrent chemoradiotherapy in esophageal squamous cell carcinoma [J]. J Immunother Cancer, 2019, 7(1): 128.
55
Dutta M, Nakagawa H, Kato H, et al. Whole genome sequencing analysis identifies recurrent structural alterations in esophageal squamous cell carcinoma [J]. Peer J, 2020, 8: e9294.
56
Cui Y, Chen H, Xi R, et al. Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma [J]. Cell Res, 2020, 30(10): 902-913.
57
王贵齐, 魏文强. 上消化道癌筛查和早诊早治项目的新转变:机会性筛查 [J]. 中华预防医学杂志, 2019, 53(11): 1084-1087.
58
Wei WQ, Hao CQ, Guan CT, et al. Esophageal Histological Precursor Lesions and Subsequent 8.5-Year Cancer Risk in a Population-Based Prospective Study in China [J]. Am J Gastroenterol, 2020, 115(7): 1036-1044.
59
Liu M, Liu Z, Cai H, et al. A Model To identify individuals at high risk for esophageal squamous cell carcinoma and precancerous lesions in regions of high prevalence in China [J]. Clin Gastroenterol Hepatol, 2017, 15(10): 1538-1546.
60
Liu M, Liu Z, Liu F, et al. Absence of iodine staining associates with progression of esophageal lesions in a prospective endoscopic surveillance study in China [J]. Clin Gastroenterol Hepatol, 2020, 18(7): 1626-1635.
61
Liu M, Zhou R, Guo C, et al. Size of Lugol-unstained lesions as a predictor for risk of progression in premalignant lesions of the esophagus [J]. Gastrointest Endosc, 2021, 93(5): 1065-1073.
62
Yip CH. Downstaging is more important than screening for asymptomatic breast cancer [J]. Lancet Glob Health, 2019, 7(6): e690-e691.
63
Wang J, Liu F, Gao H, et al. The symptom-to-treatment delay and stage at the time of treatment in cancer of esophagus [J]. Jpn J Clin Oncol, 2008, 38(2): 87-91.
64
Dos-Santos-Silva I, De Stavola BL, Renna NLJ, et al. Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001-14: a case only analysis [J]. Lancet Glob Health, 2019, 7(6): e784-e797.
65
Liu Z, Guo C, He Y, et al. A clinical model predicting the risk of esophageal high-grade lesions in opportunistic screening: a multicenter real-world study in China [J]. Gastrointest Endosc, 2020, 91(6): 1253-1260.
66
Gupta V, Coburn N, Kidane B, et al. Survival prediction tools for esophageal and gastroesophageal junction cancer: A systematic review [J]. J Thorac Cardiovasc Surg, 2018, 156(2): 847-856.
67
Deng W, Zhang W, Yang J, et al. Nomogram to predict overall survival for thoracic esophageal squamous cell carcinoma patients after radical esophagectomy [J]. Ann Surg Oncol, 2019, 26(9): 2890-2898.
68
Du F, Sun Z, Jia J, et al. Development and validation of an individualized nomogram for predicting survival in patients with esophageal carcinoma after resection [J]. J Cancer, 2020, 11(14): 4023-4029.
69
Liu F, Zhou R, Jiang F, et al. Proposal of a nomogram for predicting survival in patients with siewert type II adenocarcinoma of the esophagogastric junction after preoperative radiation [J]. Ann Surg Oncol, 2019, 26(5): 1292-1300.
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