AUTHOR=Gao Shen , Wei Guojiang , Ma Qianwang , Wang Xue , Wang Sen , Niu Yuanjie TITLE=Causal relationship between anti-inflammatory drugs and cancer: a pan-cancer study with Mendelian randomization JOURNAL=Frontiers in Genetics VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1392745 DOI=10.3389/fgene.2024.1392745 ISSN=1664-8021 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.