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Randomized Controlled Trial
. 2025 Sep 1;117(9):1875-1882.
doi: 10.1093/jnci/djaf145.

Association of non-steroidal anti-inflammatory medications and aspirin with colorectal cancer incidence in older adults

Farzana Y Zaman  1 , Suzanne G Orchard  2 , Galina Polekhina  2 , Peter Gibbs  3   4 , Wendy B Bernstein  5   6 , Finlay Macrae  7 , Jeanne Tie  3   4   8 , Jeremy Millar  2 , Lucy Gately  1   3 , Luz María Rodríguez  9   10 , Gijsberta J van Londen  9 , Victoria Mar  2   11 , Emma Hiscutt  2   11 , Nikki Adler  2   11 , Aaron Kent  12 , Wee Loon Ong  2   12 , Andrew Haydon  1   2 , Erica Warner  13 , Andrew T Chan  13 , John Zalcberg  1   2
Affiliations
Randomized Controlled Trial

Association of non-steroidal anti-inflammatory medications and aspirin with colorectal cancer incidence in older adults

Farzana Y Zaman et al. J Natl Cancer Inst. .

Abstract

Background: The relationship between aspirin, and/or other non-steroidal anti-inflammatory drugs (NSAIDs), and colorectal cancer (CRC) risk in older adults is uncertain. This study investigated the association between non-aspirin NSAIDs (NA-NSAIDs) use, alone or combined with aspirin, on CRC incidence in older adults.

Methods: This is a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial data and its observational continuation, ASPREE-XT (median follow-up, 8.4 years [IQR: 7.2-9.6]). NA-NSAID exposure was ascertained by self-report and medical record review at baseline, for all ASPREE participants, and for Australian participants, via linkage to the Pharmaceutical Benefits Scheme (PBS). CRC was an adjudicated secondary endpoint of ASPREE. We investigated the association between NA-NSAID use alone, and in combination with randomized aspirin use, on the incidence of CRC in time-to-event analyses.

Results: Of 19 114 ASPREE participants, 2713 (14%) reported NA-NSAID use at baseline. NA-NSAID use was associated with a reduced incidence of CRC (HRNA-NSAID use: Yes vs No = 0.74; 95% CI = 0.56 to 0.98). This association between NA-NSAIDs and CRC was not modified by aspirin (P-value for interaction term of 0.81). When assessing NA-NSAID use over 2 years post-randomization in Australian participants who consented to the use of PBS data (n = 13 725), a similar reduction in CRC risk was observed (HRHigh NA-NSAID use vs None = 0.52, 95% CI = 0.32 to 0.83).

Conclusions: NA-NSAID use in Australian and American adults over the age of 70 years was associated with a reduced CRC incidence, which increased with increasing exposure. Aspirin did not modify the effect of NA-NSAIDs on CRC incidence.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Cumulative incidence of CRC by NA-NSAID use at baseline and randomized treatment.
Figure 2.
Figure 2.
Cumulative incidence of CRC by PBS-NA-NSAID use category, with a time reset at 2-years post-randomization.
See this image and copyright information in PMC

References

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