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Proguanil and atovaquone use is associated with lower colorectal cancer risk : a nationwide cohort study

Zhang, Naiqi LU ; Sundquist, Jan LU ; Sundquist, Kristina LU and Ji, Jianguang LU orcid (2022) In BMC Medicine 20(1).
Abstract

Background: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical studies suggest that the anti-malaria drug proguanil and atovaquone might play a role in preventing CRC, but population-based evidence is still lacking. Methods: By accessing a couple of nationwide Swedish registers, we performed a cohort study to explore whether using proguanil and atovaquone might associate with a lower risk of CRC by adopting a new-user study design. Adults who have 1 or more first-degree relatives (parents or siblings) diagnosed with CRC were identified and linked with the Prescribed Drug Register to evaluate their administration history of proguanil and atovaquone. Survival analysis of the time... (More)

Background: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical studies suggest that the anti-malaria drug proguanil and atovaquone might play a role in preventing CRC, but population-based evidence is still lacking. Methods: By accessing a couple of nationwide Swedish registers, we performed a cohort study to explore whether using proguanil and atovaquone might associate with a lower risk of CRC by adopting a new-user study design. Adults who have 1 or more first-degree relatives (parents or siblings) diagnosed with CRC were identified and linked with the Prescribed Drug Register to evaluate their administration history of proguanil and atovaquone. Survival analysis of the time to CRC diagnosis with Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 16,817 incident proguanil/atovaquone users were identified and matched with 168,170 comparisons, who did not use proguanil/atovaquone, on the ratio of 1:10. We found a significant negative association between proguanil/atovaquone use and risk of CRC (adjusted HR, 0.76; 95% CI, 0.62–0.93). Test for trend showed significant dose- and duration-response correlations (P < 0.001). The association was more pronounced in CRC diagnosed at an advanced stage than at an early stage (adjusted HR, 0.69 vs.0.81). Conclusions: This national-wide population-based cohort study showed that the use of proguanil and atovaquone was associated with a reduced risk of CRC among individuals with a family history of CRC.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atovaquone, Chemoprevention, Colorectal cancer, Family history, Proguanil
in
BMC Medicine
volume
20
issue
1
article number
439
publisher
BioMed Central (BMC)
external identifiers
  • pmid:36357883
  • scopus:85141570104
ISSN
1741-7015
DOI
10.1186/s12916-022-02643-3
project
Drug repositioning in chemoprevention of colorectal cancer
language
English
LU publication?
yes
additional info
Funding Information: Open access funding provided by Lund University. This work was supported by grants awarded to JJ by the Swedish Research Council (2021-01187), Cancerfonden (CAN2017/340), Crafoordska Stiftelsen and Allm¨anna Sjukhusets i Malm¨o Stiftelsen f¨or bek¨ampande av cancer; to KS (2018-02400) by the Swedish Research Council; to JS (2020-01175) by the Swedish Research Council as well as by ALF funding from Region Sk°ane awarded to KS and JJ; and to NZ by China Scholarship Council (Grant No. 201906380063). Publisher Copyright: © 2022, The Author(s).
id
6b7cc6ac-7db5-4823-baea-6e425c6712ce
date added to LUP
2022-12-01 13:21:34
date last changed
2024-04-18 04:41:35
@article{6b7cc6ac-7db5-4823-baea-6e425c6712ce,
  abstract     = {{<p>Background: Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical studies suggest that the anti-malaria drug proguanil and atovaquone might play a role in preventing CRC, but population-based evidence is still lacking. Methods: By accessing a couple of nationwide Swedish registers, we performed a cohort study to explore whether using proguanil and atovaquone might associate with a lower risk of CRC by adopting a new-user study design. Adults who have 1 or more first-degree relatives (parents or siblings) diagnosed with CRC were identified and linked with the Prescribed Drug Register to evaluate their administration history of proguanil and atovaquone. Survival analysis of the time to CRC diagnosis with Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 16,817 incident proguanil/atovaquone users were identified and matched with 168,170 comparisons, who did not use proguanil/atovaquone, on the ratio of 1:10. We found a significant negative association between proguanil/atovaquone use and risk of CRC (adjusted HR, 0.76; 95% CI, 0.62–0.93). Test for trend showed significant dose- and duration-response correlations (P &lt; 0.001). The association was more pronounced in CRC diagnosed at an advanced stage than at an early stage (adjusted HR, 0.69 vs.0.81). Conclusions: This national-wide population-based cohort study showed that the use of proguanil and atovaquone was associated with a reduced risk of CRC among individuals with a family history of CRC.</p>}},
  author       = {{Zhang, Naiqi and Sundquist, Jan and Sundquist, Kristina and Ji, Jianguang}},
  issn         = {{1741-7015}},
  keywords     = {{Atovaquone; Chemoprevention; Colorectal cancer; Family history; Proguanil}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Medicine}},
  title        = {{Proguanil and atovaquone use is associated with lower colorectal cancer risk : a nationwide cohort study}},
  url          = {{http://dx.doi.org/10.1186/s12916-022-02643-3}},
  doi          = {{10.1186/s12916-022-02643-3}},
  volume       = {{20}},
  year         = {{2022}},
}