Paracetamol Intake and Hematologic Malignancies: A Meta-Analysis of Observational Studies

Hematologic malignancies cause more than half a million deaths every year worldwide. Analgesics were suggested as chemopreventive agents for several cancers but so far, results from individual studies about the relationship between paracetamol (acetaminophen) use and hematologic malignancies are conflicting. Therefore, we decided to perform a systematic review and meta-analysis. We retrieved studies published in any language by systematically searching Medline, Embase, Conference Proceedings Citation Index, Open Access Theses and Dissertations, and the five regional bibliographic databases of the World Health Organization until December 2020. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated according to the inverse of their variances. We performed separate analyses by histologic type. We also evaluated publication bias and assessed quality. A total of 17 study units met our inclusion criteria. The results show an association of hematologic malignancies with any paracetamol intake (OR 1.49, 95% CI 1.23-1.80) and with high paracetamol intake (OR 1.77, 95% CI 1.45-2.16). By subtype, risk was higher for multiple myeloma (OR 2.13, 95% CI 1.54-2.94) for any use and OR 3.16, 95% CI 1.96-5.10 for high intake, while risk was lower and non-significant for non-Hodgkin lymphoma. This meta-analysis provides evidence that paracetamol intake may be associated with hematologic malignancies and suggests that a dose-response effect is plausible. These results are unlikely to be due to publication bias or low quality of studies. Future research should focus on assessing the dose-response relationship.