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Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer : A Nested Case-Control Study

Zhang, Naiqi LU ; Sundquist, Jan LU ; Sundquist, Kristina LU ; Zhang, Zhi-Gang LU and Ji, Jianguang LU orcid (2021) In The American journal of gastroenterology 116(6). p.1313-1321
Abstract

INTRODUCTION: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC.

METHODS: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs)... (More)

INTRODUCTION: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC.

METHODS: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model.

RESULTS: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern.

DISCUSSION: This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The American journal of gastroenterology
volume
116
issue
6
pages
1313 - 1321
publisher
Wolters Kluwer
external identifiers
  • scopus:85107711829
  • pmid:33661146
ISSN
1572-0241
DOI
10.14309/ajg.0000000000001192
project
Drug repositioning in chemoprevention of colorectal cancer
language
English
LU publication?
yes
id
82f6ad40-2e07-4099-ad66-28e4303efdbe
date added to LUP
2021-03-11 10:35:26
date last changed
2024-03-21 03:43:44
@article{82f6ad40-2e07-4099-ad66-28e4303efdbe,
  abstract     = {{<p>INTRODUCTION: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC.</p><p>METHODS: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model.</p><p>RESULTS: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P &lt; 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern.</p><p>DISCUSSION: This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.</p>}},
  author       = {{Zhang, Naiqi and Sundquist, Jan and Sundquist, Kristina and Zhang, Zhi-Gang and Ji, Jianguang}},
  issn         = {{1572-0241}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{1313--1321}},
  publisher    = {{Wolters Kluwer}},
  series       = {{The American journal of gastroenterology}},
  title        = {{Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer : A Nested Case-Control Study}},
  url          = {{http://dx.doi.org/10.14309/ajg.0000000000001192}},
  doi          = {{10.14309/ajg.0000000000001192}},
  volume       = {{116}},
  year         = {{2021}},
}