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Paracetamol Intake and Hematologic Malignancies
Hematologic malignancies are a heterogeneous group of diseases of diverse incidence, prognosis, and etiology that cause 1.3 million cases and more than 700,000 deaths every year worldwide. These malignancies show a stable trend in the last decades, but an increased incidence is observed for myeloma in women.
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.
2. Hematologic Malignancies
The entry is from 10.3390/jcm10112429
- International Agency for Resarch on Cancer. World Fact Sheets. Globocan 2020. Available online: (accessed on 28 May 2021).
- Henley, S.J.; Ward, E.M.; Scott, S.; Ma, J.; Anderson, R.N.; Bs, A.U.F.; Thomas, C.C.; Islami, F.; Weir, H.K.; Lewis, D.R.; et al. Annual report to the nation on the status of cancer, part I: National cancer statistics. Cancer 2020, 126, 2225–2249.
- Takkouche, B.; Regueira-Méndez, C.; Etminan, M. Breast cancer and use of non-steroidal anti-inflammatory drugs: A meta-analysis. J. Natl. Cancer Inst. 2008, 100, 1439–1447.
- Harris, R.E. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of can-cers of the colon, breast, prostate, and lung. Inflammopharmacology 2009, 17, 55–67.
- Mantovani, A.; Allavena, P.; Sica, A.; Balkwill, F.R. Cancer-related inflammation. Nature 2008, 454, 436–444.
- Catella-Lawson, F.; Reilly, M.P.; Kapoor, S.C.; Cucchiara, A.J.; DeMarco, S.R.N.; Tournier, B.R.N.; Vyas, S.N.; FitzGerald, G.A. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N. Engl. J. Med. 2001, 345, 1809–1817.
- IARC. Phenacetin. In IARC Monograph Evaluation Carcinogenic Risk to Humans; IARC: Lyon, France, 1980; Volume 24, pp. 135–161.
- Choueiri, T.K.; Je, Y.; Cho, E. Analgesic use and the risk of kidney cancer: A meta-analysis of epidemiologic studies. Int. J. Cancer 2014, 134, 384–396.
- Jeter, J.M.; Han, J.; Martinez, M.E.; Alberts, D.S.; Qureshi, A.A.; Feskanich, D. Non-steroidal anti-inflammatory drugs, acetaminophen, and risk of skin cancer in the Nurses’ Health Study. Cancer Causes Control 2012, 23, 1451–1461.
- IARC. Paracetamol. In IARC Monograph Evaluation Carcinogenic Risk to Humans; IARC: Lyon, France, 1999; Volume 73, pp. 401–449.
- Robak, P.; Smolewski, P.; Robak, T. The role of non-steroidal anti-inflammatory drugs in the risk of development and treatment of hematologic malignancies. Leuk. Lymphoma 2008, 49, 1452–1462.
- Weiss, N.S. Use of acetaminophen in relation to the occurrence of cancer: A re-view of epidemiologic studies. Cancer Causes Control 2016, 27, 1411–1418.
- U.S. Food and Drug Administration. Don´t Double Up on Acetaminophen. Available online: (accessed on 28 May 2021).
- Duong, M.; Gulmez, S.E.; Salvo, F.; Abouelfath, A.; Lassalle, R.; Droz, C.; Blin, P.; Moore, N. Usage patterns of paracetamol in France. Br. J. Clin. Pharmacol. 2016, 82, 498–503.
- Rannug, U.; Holme, J.A.; Hongslo, J.K.; Srám, R. International Commission for Protection against Environmental Mutagens and Carcinogens. An evaluation of the genetic toxicity of paracetamol. Mutat. Res. 1995, 327, 179–200.
- Bender, R.P.; Lindsey, R.H., Jr.; Burden, D.A.; Osheroff, N. N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen, is a topoisomerase II poison. Biochemistry 2004, 43, 3731–3739.
- Ho, A.D.; Brado, B.; Haas, R.; Hunstein, W. Etoposide in acute leukemia. Past experience and future perspectives. Cancer 1991, 67, 281–284.
- Bergman, K.; Müller, L.; Teigen, S. The genotoxicity and carcinogenicity of paracetamol: A regulatory (re)view. Mutat. Res. 1996, 349, 263–288.
- Blazka, M.; Wilmer, J.; Holladay, S.; Wilson, R.; Luster, M. Role of Proinflammatory Cytokines in Acetaminophen Hepatotoxicity. Toxicol. Appl. Pharmacol. 1995, 133, 43–52.
- IQVIA Institute for Human Data Science. Medicine Use and Spending in the U.S.: A Review of 2017 and Outlook to 2022. 2018. Available online: (accessed on 28 May 2021).
- Friedman, G.D. Phenylbutazone, musculoskeletal disease, and leukemia. J. Chronic Dis. 1982, 35, 233–243.
- Lipworth, L.; Friis, S.; Mellemkjær, L.; Signorello, L.B.; Johnsen, S.P.; Nielsen, G.L.; McLaughlin, J.K.; Blot, W.J.; Olsen, J.H. A population-based cohort study of mortality among adults prescribed paracetamol in Denmark. J. Clin. Epidemiol. 2003, 56, 796–801.
- Chang, E.T.; Zheng, T.; Weir, E.G.; Borowitz, M.; Mann, R.B.; Spiegelman, D.; Mueller, N.E. Aspirin and the risk of Hodgkin’s lymphoma in a popula-tion-based case-control study. J. Natl. Cancer Inst. 2004, 96, 305–315.
- Baker, J.A.; Weiss, J.R.; Czuczman, M.S.; Menezes, R.J.; Ambrosone, C.B.; Moysich, K.B. Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma. Cancer Causes Control 2005, 16, 301–308.
- Weiss, J.R.; Baker, J.A.; Baer, M.R.; Menezes, R.J.; Nowell, S.; Moysich, K.B. Opposing effects of aspirin and acetaminophen use on risk of adult acute leukemia. Leuk. Res. 2006, 30, 164–169.
- Moysich, K.B.; Bonner, M.R.; Beehler, G.P.; Marshall, J.R.; Menezes, R.J.; Baker, J.A.; Weiss, J.R.; Chanan-Khan, A. Regular analgesic use and risk of multiple myeloma. Leuk. Res. 2007, 31, 547–551.
- Becker, N.; Fortuny, J.; Alvaro, T.; Nieters, A.; Maynadié, M.; Foretova, L.; Staines, A.; Brennan, P.; Boffetta, P.; Cocco, P.L.; et al. Medical history and risk of lymphoma: Results of a European case-control study (EPILYMPH). J. Cancer Res. Clin. Oncol. 2009, 135, 1099–1107.
- Kato, I.; Koenig, K.L.; Shore, R.E.; Baptiste, M.S.; Lillquist, P.P.; Frizzera, G.; Burke, J.S.; Watanabe, H. Use of anti-inflammatory and non-narcotic analgesic drugs and risk of non-Hodgkin’s lymphoma (NHL) (United States). Cancer Causes Control 2002, 13, 965–974.
- Friis, S.; Nielsen, G.L.; Mellemkjaer, L.; McLaughlin, J.K.; Thulstrup, A.M.; Blot, W.J.; Lipworth, L.; Vilstrup, H.; Olsen, J.H. Cancer risk in persons receiving prescriptions for paracetamol: A Danish cohort study. Int. J. Cancer 2002, 97, 96–101.
- Shen, J.; Gammon, M.D.; Terry, M.B.; Teitelbaum, S.L.; Neugut, A.I.; Santella, R.M. Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk. Breast Cancer Res. 2006, 8, R71.
- Greenland, S. Basic methods for sensitivity analysis of biases. Int. J. Epidemiol. 1996, 25, 1107–1116.
- Signorello, L.B.; McLaughlin, J.K.; Lipworth, L.; Friis, S.; Sørensen, H.T.; Blot, W.J. Confounding by Indication in Epidemiologic Studies of Commonly Used Analgesics. Am. J. Ther. 2002, 9, 199–205.
- Kaufman, D.W.; Kelly, J.P.; Rosenberg, L.; Anderson, T.E.; Mitchell, A.A. Recent patterns of medication use in the ambulatory adult population of the United States: The Slone survey. JAMA 2002, 287, 337–344.
- Rothman, K.J. Measures of disease frequency. In Modern Epidemiology, 1st ed.; Little, Brown & Co: Boston, MA, USA, 1986; Volume 39.