{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:44:04Z","timestamp":1790833444233,"version":"4.1.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T00:00:00Z","timestamp":1470787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T00:00:00Z","timestamp":1470787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is a public health priority to identify the adverse and non-adverse associations between pharmaceutical medications and cancer. We search for and evaluate associations between all prescribed medications and longitudinal cancer risk in participants of the Swedish Cancer Register (N\u2009=\u20099,014,975). We associated 552 different medications with incident cancer risk (any, breast, colon and prostate) during 5.5 years of follow-up (7\/1\/2005-12\/31\/2010) in two types of statistical models, time-to-event and case-crossover. After multiple hypotheses correction and replication, 141 (26%) drugs were associated with any cancer in a time-to-event analysis constraining drug exposure to 1 year before first cancer diagnosis and adjusting for history of medication use. In a case-crossover analysis, 36 drugs (7%) were associated with decreased cancer risk. 12 drugs were found in common in both analyses with concordant direction of association. We found 14, 10, 7% of all drugs associated with colon, prostate and breast cancers in time-to-event models. We only found 1, 2% and 0% for these cancers, respectively, in case-crossover analyses. Pharmacoepidemiologic analyses of cancer risk are sensitive to modeling choices and false-positive findings are a threat. Medication-wide analyses using different analytical models may help suggest consistent signals of increased cancer risk.<\/jats:p>","DOI":"10.1038\/srep31308","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T06:57:38Z","timestamp":1470812258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Systematic assessment of pharmaceutical prescriptions in association with cancer risk: a method to conduct a population-wide medication-wide longitudinal study"],"prefix":"10.1038","volume":"6","author":[{"given":"Chirag J.","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sundquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P. A.","family":"Ioannidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sundquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,10]]},"reference":[{"key":"BFsrep31308_CR1","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1001\/archinternmed.2009.306","volume":"169","author":"I Pitrou","year":"2009","unstructured":"Pitrou, I., Boutron, I., Ahmad, N. & Ravaud, P. Reporting of safety results in published reports of randomized controlled trials. Arch Intern Med 169, 1756\u20131761, 10.1001\/archinternmed.2009.306 (2009).","journal-title":"Arch Intern Med"},{"key":"BFsrep31308_CR2","doi-asserted-by":"publisher","first-page":"e124","DOI":"10.1371\/journal.pmed.0020124","volume":"2","author":"JPAWhyMost Ioannidis","year":"2005","unstructured":"Ioannidis, J. P. A. Why Most Published Research Findings Are False. PLoS Med 2, e124 (2005).","journal-title":"PLoS Med"},{"key":"BFsrep31308_CR3","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1097\/EDE.0b013e31818131e7","volume":"19","author":"JPA Ioannidis","year":"2008","unstructured":"Ioannidis, J. P. A. Why most discovered true associations are inflated? Epidemiology 19, 640\u2013648, 10.1097\/EDE.0b013e31818131e7 (2008).","journal-title":"Epidemiology"},{"key":"BFsrep31308_CR4","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/clpt.2012.50","volume":"91","author":"R Harpaz","year":"2012","unstructured":"Harpaz, R. et al. Novel data-mining methodologies for adverse drug event discovery and analysis. Clin Pharmacol Ther 91, 1010\u20131021, 10.1038\/clpt.2012.50 (2012).","journal-title":"Clin Pharmacol Ther"},{"key":"BFsrep31308_CR5","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1038\/psp.2013.52","volume":"2","author":"PB Ryan","year":"2013","unstructured":"Ryan, P. B., Madigan, D., Stang, P. E., Schuemie, M. J. & Hripcsak, G. Medication-Wide Association Studies. CPT: Pharmacometrics & Systems Pharmacology 2, e76, 10.1038\/psp.2013.52 (2013).","journal-title":"CPT: Pharmacometrics & Systems Pharmacology"},{"key":"BFsrep31308_CR6","doi-asserted-by":"publisher","first-page":"4401","DOI":"10.1002\/sim.5620","volume":"31","author":"PB Ryan","year":"2012","unstructured":"Ryan, P. B. et al. Empirical assessment of methods for risk identification in healthcare data: results from the experiments of the Observational Medical Outcomes Partnership. Stat Med 31, 4401\u20134415, 10.1002\/sim.5620 (2012).","journal-title":"Stat Med"},{"key":"BFsrep31308_CR7","doi-asserted-by":"publisher","first-page":"e10746","DOI":"10.1371\/journal.pone.0010746","volume":"5","author":"CJ Patel","year":"2010","unstructured":"Patel, C. J., Bhattacharya, J. & Butte, A. J. An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus. Plos One 5, e10746, 10.1371\/journal.pone.0010746 (2010).","journal-title":"Plos One"},{"key":"BFsrep31308_CR8","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1093\/ije\/dys003","volume":"41","author":"CJ Patel","year":"2012","unstructured":"Patel, C. J., Cullen, M. R., Ioannidis, J. P. & Butte, A. J. Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels. Int J Epidemiol 41, 828\u2013843, 10.1093\/ije\/dys003 (2012).","journal-title":"Int J Epidemiol"},{"key":"BFsrep31308_CR9","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1161\/CIRCULATIONAHA.112.114058","volume":"126","author":"I Tzoulaki","year":"2012","unstructured":"Tzoulaki, I. et al. A nutrient-wide association study on blood pressure. Circulation 126, 2456\u20132464, 10.1161\/CIRCULATIONAHA.112.114058 (2012).","journal-title":"Circulation"},{"key":"BFsrep31308_CR10","first-page":"1","volume":"45C","author":"CJ Patel","year":"2013","unstructured":"Patel, C. J. et al. Investigation of maternal environmental exposures in association with self-reported preterm birth. Reprod Toxicol 45C, 1\u20137 (2013).","journal-title":"Reprod Toxicol"},{"key":"BFsrep31308_CR11","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/aje\/kwu277","volume":"181","author":"CJ Patel","year":"2014","unstructured":"Patel, C. J., Cullen, M. R., Ioannidis, J. P. A. & Rehkopf, D. H. Systematic assessment of the correlation of household income with infectious, biochemical, physiological factors in the United States, 1999\u20132006. Am J Epidemiol 181, 171\u2013179 (2014).","journal-title":"Am J Epidemiol"},{"key":"BFsrep31308_CR12","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1093\/ije\/dyt208","volume":"42","author":"CJ Patel","year":"2013","unstructured":"Patel, C. J. et al. Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey. Int J Epidemiol 42, 1795\u20131810, 10.1093\/ije\/dyt208 (2013).","journal-title":"Int J Epidemiol"},{"key":"BFsrep31308_CR13","doi-asserted-by":"crossref","unstructured":"Ioannidis, J. P. et al. Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses. Ann Oncol, 10.1093\/annonc\/mdt372 (2013).","DOI":"10.1093\/annonc\/mdt372"},{"key":"BFsrep31308_CR14","unstructured":"European Network of Centres for Pharmacoepidemiology and Pharmacovigiliance. European Network of Centres for Pharmacoepidemiology and Pharmacovigiliance (ENCEPP) Checklist for Study Protocols, (http:\/\/www.encepp.eu\/standards_and_guidances\/index.shtml (2014)."},{"key":"BFsrep31308_CR15","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1111\/j.1742-7843.2009.00494.x","volume":"106","author":"K Furu","year":"2010","unstructured":"Furu, K. et al. The Nordic countries as a cohort for pharmacoepidemiological research. Basic Clin Pharmacol Toxicol 106, 86\u201394, 10.1111\/j.1742-7843.2009.00494.x (2010).","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"BFsrep31308_CR16","unstructured":"WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment (World Health Organization, 2014)."},{"key":"BFsrep31308_CR17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57, 289\u2013300 (1995).","journal-title":"J R Stat Soc B"},{"key":"BFsrep31308_CR18","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1056\/NEJM199312023292301","volume":"329","author":"MA Mittleman","year":"1993","unstructured":"Mittleman, M. A. et al. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med 329, 1677\u20131683, 10.1056\/NEJM199312023292301 (1993).","journal-title":"N Engl J Med"},{"key":"BFsrep31308_CR19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1146\/annurev.publhealth.21.1.193","volume":"21","author":"M Maclure","year":"2000","unstructured":"Maclure, M. & Mittleman, M. A. Should we use a case-crossover design? Annu Rev Public Health 21, 193\u2013221, 10.1146\/annurev.publhealth.21.1.193 (2000).","journal-title":"Annu Rev Public Health"},{"key":"BFsrep31308_CR20","unstructured":"R: A language for statistical computing v. 2.8.1 (R Foundation for Statistical Computing, Vienna, Austria, 2009)."},{"key":"BFsrep31308_CR21","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/sim.5925","volume":"33","author":"MJ Schuemie","year":"2014","unstructured":"Schuemie, M. J., Ryan, P. B., Dumouchel, W., Suchard, M. A. & Madigan, D. Interpreting observational studies: why empirical calibration is needed to correct p-values. Stat Med 33, 209\u2013218, 10.1002\/sim.5925 (2014).","journal-title":"Stat Med"},{"key":"BFsrep31308_CR22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/biostatistics\/kxt037","volume":"15","author":"MJ Schuemie","year":"2014","unstructured":"Schuemie, M. J., Ryan, P. B., Suchard, M. A., Shahn, Z. & Madigan, D. Discussion: An estimate of the science-wise false discovery rate and application to the top medical literature. Biostatistics 15, 36\u201339, 10.1093\/biostatistics\/kxt037 (2014).","journal-title":"Biostatistics"},{"key":"BFsrep31308_CR23","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1001\/jama.2012.96867","volume":"309","author":"V Prasad","year":"2013","unstructured":"Prasad, V. & Jena, A. B. Prespecified falsification end points: can they validate true observational associations? J Am Med Assoc 309, 241\u2013242, 10.1001\/jama.2012.96867 (2013).","journal-title":"J Am Med Assoc"},{"key":"BFsrep31308_CR24","doi-asserted-by":"publisher","first-page":"e0149144","DOI":"10.1371\/journal.pone.0149144","volume":"11","author":"SB Bruns","year":"2016","unstructured":"Bruns, S. B. & Ioannidis, J. P. p-Curve and p-Hacking in Observational Research. PLoS One 11, e0149144, 10.1371\/journal.pone.0149144 (2016).","journal-title":"PLoS One"},{"key":"BFsrep31308_CR25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1177\/0962280208092346","volume":"18","author":"JA Delaney","year":"2009","unstructured":"Delaney, J. A. & Suissa, S. The case-crossover study design in pharmacoepidemiology. Stat Methods Med Res 18, 53\u201365, 10.1177\/0962280208092346 (2009).","journal-title":"Stat Methods Med Res"},{"key":"BFsrep31308_CR26","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1002\/sim.6825","volume":"35","author":"JP Ioannidis","year":"2016","unstructured":"Ioannidis, J. P. Exposure-wide epidemiology: revisiting Bradford Hill. Stat Med 35, 1749\u20131762, 10.1002\/sim.6825 (2016).","journal-title":"Stat Med"},{"key":"BFsrep31308_CR27","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1097\/EDE.0b013e318228ca1d","volume":"22","author":"D Madigan","year":"2011","unstructured":"Madigan, D. & Ryan, P. What can we really learn from observational studies? the need for empirical assessment of methodology for active drug safety surveillance and comparative effectiveness research. Epidemiology 22, 629\u2013631, 10.1097\/EDE.0b013e318228ca1d (2011).","journal-title":"Epidemiology"},{"key":"BFsrep31308_CR28","doi-asserted-by":"crossref","unstructured":"Mittal, S., Madigan, D., Burd, R. S. & Suchard, M. A. High-dimensional, massive sample-size Cox proportional hazards regression for survival analysis. Biostatistics, 10.1093\/biostatistics\/kxt043 (2013).","DOI":"10.1093\/biostatistics\/kxt043"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep31308","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31308.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep31308.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T16:24:52Z","timestamp":1718727892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep31308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,10]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,11,14]]}},"alternative-id":["BFsrep31308"],"URL":"https:\/\/doi.org\/10.1038\/srep31308","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,10]]},"assertion":[{"value":"11 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 July 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31308"}}