Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 24:15:1392745.
doi: 10.3389/fgene.2024.1392745. eCollection 2024.

Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization

Shen Gao #  1   2 , Guojiang Wei #  1   2 , Qianwang Ma  1   2 , Xue Wang  1   2 , Sen Wang  3 , Yuanjie Niu  1   2
Affiliations

Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization

Shen Gao et al. Front Genet. .

Abstract

Background: Numerous epidemiological studies have elucidated the intricate connection between inflammation and cancer, highlighting how sustained inflammatory responses can fuel carcinogenesis by fostering proliferation, angiogenesis, and metastasis, while dampening immune responses and sensitivity to chemotherapy. Previous clinical investigations have underscored the potential of anti-inflammatory medications in either preventing or mitigating tumor formation. Here, the causal relationship between anti-inflammatory drugs and cancer was further explored through Mendelian randomization studies.

Methods: Employing Mendelian randomization, we scrutinized the causal links between three anti-inflammatory drugs-NSAIDs, Aspirin, and Anilide-and 37 types of cancer. We primarily utilized inverse variance weighting (IVW) as the primary analytical approach to delineate the causal association between these drugs and cancer types. Concurrently, sensitivity analyses were conducted to ascertain the absence of horizontal pleiotropy and heterogeneity.

Results: Our investigation revealed a discernible causal relationship between certain anti-inflammatory drugs and a subset of cancers, albeit without a pervasive impact across all cancer types. Specifically, NSAIDs exhibited a risk-reducing effect on non-small cell lung cancer (OR: 0.76, 95% CI: 0.59-0.97, p-value: 0.03) and gastric cancer (OR: 0.57, 95% CI: 0.34-0.98, p-value: 0.04). Conversely, aspirin was associated with an increased risk of oral malignant tumors (OR: 2.18, 95% CI: 1.13-4.21, p-value: 0.02). Notably, no statistically significant findings were observed for anilide drugs (p < 0.05).

Conclusion: We identified several cancers with potential causal links to NSAIDs, including non-small cell lung cancer and gastric cancer. Despite our extensive analysis, we did not identify a substantial causal relationship between the use of anti-inflammatory drugs and the development of various cancers.

Keywords: Mendelian randomization analysis; NSAIDs; anilide; anti-inflammatory medications; aspirin; pancancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of Mendelian randomization analysis in this study.
FIGURE 2
FIGURE 2
Forest plot of statistically significant summary results in Mendelian randomization analysis of anti-inflammatory drugs and cancer (p < 0.05).
FIGURE 3
FIGURE 3
Forest plot of Mendelian randomization analysis results between NSAIDs and various cancers.
FIGURE 4
FIGURE 4
Forest plot of results from Mendelian randomization analysis between aspirin and various cancers.
FIGURE 5
FIGURE 5
Forest plot of results from Mendelian randomization analysis between anilide drugs and various cancers.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Arico S., Pattingre S., Bauvy C., Gane P., Barbat A., Codogno P., et al. (2002). Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J. Biol. Chem. 277, 27613–27621. 10.1074/jbc.M201119200 - DOI - PubMed
    1. Arunasree K. M., Roy K. R., Anilkumar K., Aparna A., Reddy G. V., Reddanna P. (2008). Imatinib-resistant K562 cells are more sensitive to celecoxib, a selective COX-2 inhibitor: role of COX-2 and MDR-1. Leuk. Res. 32, 855–864. 10.1016/j.leukres.2007.11.007 - DOI - PubMed
    1. Ayoub S. S. (2021). Paracetamol (acetaminophen): a familiar drug with an unexplained mechanism of action. Temp. (Austin) 8, 351–371. 10.1080/23328940.2021.1886392 - DOI - PMC - PubMed
    1. Balkwill F., Mantovani A. (2001). Inflammation and cancer: back to Virchow? Lancet 357, 539–545. 10.1016/S0140-6736(00)04046-0 - DOI - PubMed
    1. Bindu S., Mazumder S., Bandyopadhyay U. (2020). Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem. Pharmacol. 180, 114147. 10.1016/j.bcp.2020.114147 - DOI - PMC - PubMed

LinkOut - more resources