| Literature DB >> 34663923 |
Sarah Moody1, Sergey Senkin2, S M Ashiqul Islam3,4,5, Jingwei Wang1, Dariush Nasrollahzadeh2,6, Ricardo Cortez Cardoso Penha2, Stephen Fitzgerald1, Erik N Bergstrom3,4,5, Joshua Atkins2, Yudou He3,4,5, Azhar Khandekar3,4,5, Karl Smith-Byrne2, Christine Carreira7, Valerie Gaborieau2, Calli Latimer1, Emily Thomas1, Irina Abnizova1, Pauline E Bucciarelli1, David Jones1, Jon W Teague1, Behnoush Abedi-Ardekani2, Stefano Serra8, Jean-Yves Scoazec9, Hiva Saffar10, Farid Azmoudeh-Ardalan11, Masoud Sotoudeh6, Arash Nikmanesh6, Hossein Poustchi6, Ahmadreza Niavarani6, Samad Gharavi6, Michael Eden12, Paul Richman13, Lia S Campos14, Rebecca C Fitzgerald15, Luis Felipe Ribeiro16, Sheila Coelho Soares-Lima16, Charles Dzamalala17, Blandina Theophil Mmbaga18, Tatsuhiro Shibata19, Diana Menya20, Alisa M Goldstein21, Nan Hu21, Reza Malekzadeh6, Abdolreza Fazel22, Valerie McCormack23, James McKay2, Sandra Perdomo2, Ghislaine Scelo2,24, Estelle Chanudet2, Laura Humphreys1, Ludmil B Alexandrov3,4,5, Paul Brennan2, Michael R Stratton25.
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.Entities:
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Year: 2021 PMID： 34663923 DOI： 10.1038/s41588-021-00928-6
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330