NSAID use and somatic exomic mutations in Barrett's esophagus

Genome Medicine
Patricia C GalipeauXiaohong Li

Abstract

Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to protect against tetraploidy, aneuploidy, and chromosomal alterations in the metaplastic condition Barrett's esophagus (BE) and to lower the incidence and mortality of esophageal adenocarcinoma (EA). The esophagus is exposed to both intrinsic and extrinsic mutagens resulting from gastric reflux, chronic inflammation, and exposure to environmental carcinogens such as those found in cigarettes. Here we test the hypothesis that NSAID use inhibits accumulation of point mutations/indels during somatic genomic evolution in BE. Whole exome sequences were generated from 82 purified epithelial biopsies and paired blood samples from a cross-sectional study of 41 NSAID users and 41 non-users matched by sex, age, smoking, and continuous time using or not using NSAIDs. NSAID use reduced overall frequency of point mutations across the spectrum of mutation types, lowered the frequency of mutations even when adjusted for both TP53 mutation and smoking status, and decreased the prevalence of clones with high variant allele frequency. Never smokers who consistently used NSAIDs had fewer point mutations in signature 17, which is commonly found in EA. NSAID us...Continue Reading

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Citations

Aug 25, 2019·Nature Communications·Wa Xian, Frank McKeon
Nov 6, 2018·Frontiers in Immunology·Ibrahim Al BakirTrevor A Graham
Mar 15, 2019·Genome Medicine·Patricia C GalipeauXiaohong Li
May 1, 2021·Pathogens·Risa NakanishiHiroyuki Marusawa
Nov 4, 2021·Nature Reviews. Gastroenterology & Hepatology·Melissa SchmidtTrevor A Graham

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Methods Mentioned

BETA
deamination
exome sequencing
biopsies
biopsy

Software Mentioned

BWA
AspECT
MuTect
Strelka
ADTEx
Network Exchange
deconstructSigs

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