ArticleNature genetics2021
Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence.
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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108citing papers in PubMed, 1 pooled it
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.
- The carcinogenicity of opium consumption: a systematic review and meta-analysis.European journal of epidemiology · 2023Pooled it
- The urgent challenge of gastroesophageal cancer.Nature reviews. Cancer · 2026Article
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- Centralized processing of frozen tumor tissues for global cancer genomics.Nature protocols · 2026Review
- Identification and validation of a previously missed mutational signature in colorectal cancer.Nature communications · 2026Article
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- Effects of ethanol and acetaldehyde on multi-organ genomic mutation landscapes.Cell biology and toxicology · 2026Article
- Needle-shaped diatom frustules in food as a possible promoter of esophageal squamous cell carcinoma in coastal southeastern China: A pilot study.International journal of cancer · 2026Article
- Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns.International journal of oral science · 2026Article
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Enrichment of T: A→A: T substitutions in the TP53 gene in esophageal carcinoma with high Fusobacterium burden.Scientific reports · 2026Article
- Tumour promotion through the lens of evolution.Nature · 2026Review
- A signature-agnostic test for differences between tumor mutation spectra reveals carcinogen and ancestry effects.Communications biology · 2026Article
- Ethnic genomic diversity in esophageal squamous cell carcinoma.World journal of gastrointestinal oncology · 2026Review
- Long-term exposure to the ethanol-derived metabolite acetaldehyde elevates structural genomic alterations but not base substitutions.Communications biology · 2026Article
- Reshaping immune cell distribution with mRNA noncationic lipid nanoparticles for overcoming neoadjuvant chemo-immunotherapy resistance.Theranostics · 2026Article
- The Mutational Epidemiology of Childhood Cancer.Clinical chemistry · 2025Review
- Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.Cellular and molecular life sciences : CMLS · 2025Review
- A Risk Prognostic Signature Basing on Cuproptosis-related Ferroptosis and Immune Genes for Esophageal Squamous Cell Carcinoma Patients.Cell biochemistry and biophysics · 2025Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
53 authors at 18 institutions in 11 countries.
Sarah Moody *Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-4904-1041
Sergey Senkin *Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0001-5848-005X
S M Ashiqul IslamMoores Cancer Centre, UC San Diego Health, La Jolla, CA, USA.
Jingwei WangCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-0201-2369
Dariush NasrollahzadehGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Ricardo Cortez Cardoso PenhaGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Stephen FitzgeraldCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Erik N BergstromMoores Cancer Centre, UC San Diego Health, La Jolla, CA, USA.
Joshua AtkinsGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Yudou HeMoores Cancer Centre, UC San Diego Health, La Jolla, CA, USA.
Azhar KhandekarMoores Cancer Centre, UC San Diego Health, La Jolla, CA, USA.
Karl Smith-ByrneGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0002-1932-7463
Christine CarreiraEvidence Synthesis and Classification Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Valerie GaborieauGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Calli LatimerCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Emily ThomasCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-4563-8695
Irina AbnizovaCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Pauline E BucciarelliCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
David JonesCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.ORCID http://orcid.org/0000-0002-0407-0386
Jon W TeagueCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Behnoush Abedi-ArdekaniGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0002-0980-0587
Stefano SerraUniversity Health Network, Toronto, Ontario, Canada.
Jean-Yves ScoazecDepartment Laboratory Medicine and Pathology, Gustave Roussy, Paris, France.
Hiva SaffarDepartment of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Farid Azmoudeh-ArdalanLiver Transplantation Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Masoud SotoudehDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Arash NikmaneshDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Hossein PoustchiDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Ahmadreza NiavaraniDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Samad GharaviDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.
Michael EdenCambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, UK.
Paul RichmanHistopathology Department, Hemel Hempstead General Hospital, Hemel Hempstead, UK.
Lia S CamposWest Suffolk NHS Foundation Trust, Bury St Edmunds, UK.
Rebecca C FitzgeraldMRC Cancer Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-3434-3568
Luis Felipe RibeiroBrazilian National Cancer Institute, Rio de Janeiro, Brazil.
Sheila Coelho Soares-LimaBrazilian National Cancer Institute, Rio de Janeiro, Brazil.ORCID http://orcid.org/0000-0002-6742-3708
Charles DzamalalaUniversity of Malawi, Zomba, Malawi.
Blandina Theophil MmbagaKilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre & Kilimanjaro Christian Medical University College, Moshi, Tanzania.ORCID http://orcid.org/0000-0002-5550-1916
Tatsuhiro ShibataDivision of Cancer Genomics, National Cancer Centre Research Institute, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0477-210X
Diana MenyaMoi University, Mombasa, Kenya.
Alisa M GoldsteinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.ORCID http://orcid.org/0000-0002-7538-3582
Nan HuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA.
Reza MalekzadehDigestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, Tehran, Iran.ORCID http://orcid.org/0000-0002-9820-6335
Abdolreza FazelGolestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.
Valerie McCormackEnvironment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
James McKayGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Sandra PerdomoGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Ghislaine SceloGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Estelle ChanudetGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Laura HumphreysCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Ludmil B AlexandrovMoores Cancer Centre, UC San Diego Health, La Jolla, CA, USA.
Paul BrennanGenomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.ORCID http://orcid.org/0000-0002-0518-8714
Michael R StrattonCancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK. mrs@sanger.ac.uk.ORCID http://orcid.org/0000-0001-6035-153X
Centre international de recherche sur le cancer · FRWellcome Sanger Institute · GBShariati Hospital · IRUC San Diego Health System · USInstituto Nacional de Câncer - INCA · BRNational Cancer Institute · USCambridge University Hospitals NHS Foundation Trust · GBGolestan University · IRHemel Hempstead Hospital · GBImam Khomeini Hospital · IRInstitut Gustave Roussy · FRKilimanjaro Christian Medical Centre · TZMoi University · KENational Cancer Centre Japan · JPUniversity Health Network · CAUniversity of Cambridge · GBUniversity of Malawi · MWWest Suffolk NHS Foundation Trust · GB
Funding
Esophageal cancer in West KenyaR21CA191965 · NCI · INTERNATIONAL AGENCY FOR RES ON CANCER · PI MCCORMACK, VALERIE · 2015 to 2016
$256kCancer Research UK C98/A24032Cancer Research UK RG81771/84119Medical Research Council RG84369NCI NIH HHS R21 CA191965Wellcome Trust 206194World Health Organization 001
Abstract
Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.
Indexed as
MutationAdultAgedAged, 80 and overAldehyde Dehydrogenase, MitochondrialAPOBEC DeaminasesBrazilChinaEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaFemaleHumansIncidenceIranMaleMiddle AgedAldehyde Dehydrogenase, MitochondrialALDH2 protein, humanAPOBEC DeaminasesTP53 protein, humanTumor Suppressor Protein p53
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