NSAIDs Modulate Clonal Evolution in Barrett's Esophagus

Rumen L. Kostadinov, Mary K. Kuhner, Xiaohong Li, Carissa A. Sanchez, Patricia C. Galipeau, Thomas G. Paulson, Cassandra L. Sather, Amitabh Srivastava, Robert D. Odze, Patricia L. Blount, Thomas L. Vaughan, Brian J. Reid, Carlo Maley

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5-8 time points over 6.4-19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1-8.6) off-NSAIDs and 0.6 (95% SI 0.3-1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs.

Original languageEnglish (US)
Article numbere1003553
JournalPLoS Genetics
Volume9
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Clonal Evolution
Barrett Esophagus
nonsteroidal anti-inflammatory agents
esophagus
abnormality
genomics
drug
Anti-Inflammatory Agents
Pharmaceutical Preparations
Adenocarcinoma
Genome
adenocarcinoma
Biopsy
biopsy
genome
Clone Cells
Neoplasms
neoplasms
clone
cancer

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Kostadinov, R. L., Kuhner, M. K., Li, X., Sanchez, C. A., Galipeau, P. C., Paulson, T. G., ... Maley, C. (2013). NSAIDs Modulate Clonal Evolution in Barrett's Esophagus. PLoS Genetics, 9(6), [e1003553]. https://doi.org/10.1371/journal.pgen.1003553

NSAIDs Modulate Clonal Evolution in Barrett's Esophagus. / Kostadinov, Rumen L.; Kuhner, Mary K.; Li, Xiaohong; Sanchez, Carissa A.; Galipeau, Patricia C.; Paulson, Thomas G.; Sather, Cassandra L.; Srivastava, Amitabh; Odze, Robert D.; Blount, Patricia L.; Vaughan, Thomas L.; Reid, Brian J.; Maley, Carlo.

In: PLoS Genetics, Vol. 9, No. 6, e1003553, 06.2013.

Research output: Contribution to journalArticle

Kostadinov, RL, Kuhner, MK, Li, X, Sanchez, CA, Galipeau, PC, Paulson, TG, Sather, CL, Srivastava, A, Odze, RD, Blount, PL, Vaughan, TL, Reid, BJ & Maley, C 2013, 'NSAIDs Modulate Clonal Evolution in Barrett's Esophagus', PLoS Genetics, vol. 9, no. 6, e1003553. https://doi.org/10.1371/journal.pgen.1003553
Kostadinov RL, Kuhner MK, Li X, Sanchez CA, Galipeau PC, Paulson TG et al. NSAIDs Modulate Clonal Evolution in Barrett's Esophagus. PLoS Genetics. 2013 Jun;9(6). e1003553. https://doi.org/10.1371/journal.pgen.1003553
Kostadinov, Rumen L. ; Kuhner, Mary K. ; Li, Xiaohong ; Sanchez, Carissa A. ; Galipeau, Patricia C. ; Paulson, Thomas G. ; Sather, Cassandra L. ; Srivastava, Amitabh ; Odze, Robert D. ; Blount, Patricia L. ; Vaughan, Thomas L. ; Reid, Brian J. ; Maley, Carlo. / NSAIDs Modulate Clonal Evolution in Barrett's Esophagus. In: PLoS Genetics. 2013 ; Vol. 9, No. 6.
@article{7377b418f31240dda8f0d57fb67df1b4,
title = "NSAIDs Modulate Clonal Evolution in Barrett's Esophagus",
abstract = "Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5-8 time points over 6.4-19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95{\%} support interval [SI], 7.1-8.6) off-NSAIDs and 0.6 (95{\%} SI 0.3-1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs.",
author = "Kostadinov, {Rumen L.} and Kuhner, {Mary K.} and Xiaohong Li and Sanchez, {Carissa A.} and Galipeau, {Patricia C.} and Paulson, {Thomas G.} and Sather, {Cassandra L.} and Amitabh Srivastava and Odze, {Robert D.} and Blount, {Patricia L.} and Vaughan, {Thomas L.} and Reid, {Brian J.} and Carlo Maley",
year = "2013",
month = "6",
doi = "10.1371/journal.pgen.1003553",
language = "English (US)",
volume = "9",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - NSAIDs Modulate Clonal Evolution in Barrett's Esophagus

AU - Kostadinov, Rumen L.

AU - Kuhner, Mary K.

AU - Li, Xiaohong

AU - Sanchez, Carissa A.

AU - Galipeau, Patricia C.

AU - Paulson, Thomas G.

AU - Sather, Cassandra L.

AU - Srivastava, Amitabh

AU - Odze, Robert D.

AU - Blount, Patricia L.

AU - Vaughan, Thomas L.

AU - Reid, Brian J.

AU - Maley, Carlo

PY - 2013/6

Y1 - 2013/6

N2 - Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5-8 time points over 6.4-19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1-8.6) off-NSAIDs and 0.6 (95% SI 0.3-1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs.

AB - Cancer is considered an outcome of decades-long clonal evolution fueled by acquisition of somatic genomic abnormalities (SGAs). Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce cancer risk, including risk of progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA). However, the cancer chemopreventive mechanisms of NSAIDs are not fully understood. We hypothesized that NSAIDs modulate clonal evolution by reducing SGA acquisition rate. We evaluated thirteen individuals with BE. Eleven had not used NSAIDs for 6.2±3.5 (mean±standard deviation) years and then began using NSAIDs for 5.6±2.7 years, whereas two had used NSAIDs for 3.3±1.4 years and then discontinued use for 7.9±0.7 years. 161 BE biopsies, collected at 5-8 time points over 6.4-19 years, were analyzed using 1Million-SNP arrays to detect SGAs. Even in the earliest biopsies there were many SGAs (284±246 in 10/13 and 1442±560 in 3/13 individuals) and in most individuals the number of SGAs changed little over time, with both increases and decreases in SGAs detected. The estimated SGA rate was 7.8 per genome per year (95% support interval [SI], 7.1-8.6) off-NSAIDs and 0.6 (95% SI 0.3-1.5) on-NSAIDs. Twelve individuals did not progress to EA. In ten we detected 279±86 SGAs affecting 53±30 Mb of the genome per biopsy per time point and in two we detected 1,463±375 SGAs affecting 180±100 Mb. In one individual who progressed to EA we detected a clone having 2,291±78 SGAs affecting 588±18 Mb of the genome at three time points in the last three of 11.4 years of follow-up. NSAIDs were associated with reduced rate of acquisition of SGAs in eleven of thirteen individuals. Barrett's cells maintained relative equilibrium level of SGAs over time with occasional punctuations by expansion of clones having massive amount of SGAs.

UR - http://www.scopus.com/inward/record.url?scp=84879641253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879641253&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1003553

DO - 10.1371/journal.pgen.1003553

M3 - Article

C2 - 23785299

AN - SCOPUS:84879641253

VL - 9

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 6

M1 - e1003553

ER -