Rumen Kostadinov led the analyses on the following paper which suggests that one of the mechanisms by which aspirin and other NSAIDs reduces cancer risk is through reducing the mutation rate.

PLoS Genetics. June 13, 2013, 9(6): e1003553. doi:10.1371/journal.pgen.1003553.

NSAIDs Modulate Clonal Evolution in Barrett’s Esophagus

Kostadinov RL, Kuhner MK, Sanchez CA, Galipeau PC, Paulson TG, Li X, Sather CL, Srivastava A, Odze RD, Blount PL, Vaughan TL, Reid BJ, Maley CC.


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 Summary

Cancer is a disease that develops over decades as result of accumulation of abnormalities in the genomes of otherwise normal cells. Cells in tumors compete for space and resources. Those cells able to survive the Darwinian struggle for existence within tissues progressively evolve uncontrolled growth and in some cases this results in cancer. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) reduce death rate from multiple types of cancer by about 20%. However, the mechanisms by which NSAIDs act to prevent cancer are not fully understood. By examining thirteen individuals with Barrett’s esophagus over time, we showed that the rate of accumulation of genomic abnormalities decreased when most individuals started taking NSAIDs. We also observed that, surprisingly, the number of abnormalities in the Barrett’s tissues did not increase much over decades. However, in one individual who progressed to esophageal cancer, we observed massive genomic abnormalities affecting 19% of the genome. These findings suggest that NSAIDs may prevent cancer by reducing the accumulation of genomic abnormalities over time and that detection of stable versus unstable genomes may be used in the clinic to help manage treatment options in Barrett’s esophagus.