Increased Cancer Risk From Commonly Used Medications
Increased Cancer Risk From Commonly Used Medications
Several commonly used medications have been associated with increased cancer risk in the literature. Here, we evaluated the strength and consistency of these claims in published meta-analyses. We carried out an umbrella review of 74 meta-analysis articles addressing the association of commonly used medications (antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and others) with cancer risk where at least one meta-analysis in the medication class included some data from randomized trials. Overall, 51 articles found no statistically significant differences, 13 found some decreased cancer risk, and 11 found some increased risk (one reported both increased and decreased risks). The 11 meta-analyses that found some increased risks reported 16 increased risk estimates, of which 5 pertained to overall cancer and 11 to site-specific cancer. Six of the 16 estimates were derived from randomized trials and 10 from observational data. Estimates of increased risk were strongly inversely correlated with the amount of evidence (number of cancer cases) (Spearman's correlation coefficient = −0.77, P < 0.001). In 4 of the 16 topics, another meta-analysis existed that was larger (n = 2) or included better controlled data (n = 2) and in all 4 cases there was no statistically significantly increased risk of malignancy. No medication or class had substantial and consistent evidence for increased risk of malignancy. However, for most medications we cannot exclude small risks or risks in population subsets. Such risks are unlikely to be possible to document robustly unless very large, collaborative studies with standardized analyses and no selective reporting are carried out.
A number of commonly used medications have been associated with increased risk of malignancy in diverse studies. Such cancer risks are very important to document, if present, because the use of commonly used drugs and biologics continues to increase and the resulting burden of disease due to malignancy can be substantial at the population level. However, for most of the proposed pharmacoepidemiological links of cancer, there has been substantial controversy about their validity and often investigations with varying study designs and populations have arrived at different conclusions. For some of these associations, there are already a very large number of studies and even several meta-analyses thereof. However, even meta-analyses on the same topic may reach contradicting results and conclusions.
In this umbrella review, we aimed to collect systematically and critically reassess the results of meta-analyses of common medications that have been associated with increased cancer risk. We aimed to juxtapose the results of meta-analyses on similar drugs and cancer types to see how much they agree or disagree, to understand why disagreements may have arisen, and try to decipher eventually the presence or absence of cancer risks for these pharmacological and biological agents. We examined those associations where there is at least one meta-analysis, including data from randomized trials. For those topics, we evaluated all meta-analyses, regardless of whether they included randomized trials or observational data. We examined in depth those associations where at least one meta-analysis has claimed any nominally statistically significant increased cancer risk. We aimed to see how strong and consistent the evidence was for these claims of significant cancer risks across different types of study designs and different meta-analyses on the same or similar topic.
Abstract and Introduction
Abstract
Several commonly used medications have been associated with increased cancer risk in the literature. Here, we evaluated the strength and consistency of these claims in published meta-analyses. We carried out an umbrella review of 74 meta-analysis articles addressing the association of commonly used medications (antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and others) with cancer risk where at least one meta-analysis in the medication class included some data from randomized trials. Overall, 51 articles found no statistically significant differences, 13 found some decreased cancer risk, and 11 found some increased risk (one reported both increased and decreased risks). The 11 meta-analyses that found some increased risks reported 16 increased risk estimates, of which 5 pertained to overall cancer and 11 to site-specific cancer. Six of the 16 estimates were derived from randomized trials and 10 from observational data. Estimates of increased risk were strongly inversely correlated with the amount of evidence (number of cancer cases) (Spearman's correlation coefficient = −0.77, P < 0.001). In 4 of the 16 topics, another meta-analysis existed that was larger (n = 2) or included better controlled data (n = 2) and in all 4 cases there was no statistically significantly increased risk of malignancy. No medication or class had substantial and consistent evidence for increased risk of malignancy. However, for most medications we cannot exclude small risks or risks in population subsets. Such risks are unlikely to be possible to document robustly unless very large, collaborative studies with standardized analyses and no selective reporting are carried out.
Introduction
A number of commonly used medications have been associated with increased risk of malignancy in diverse studies. Such cancer risks are very important to document, if present, because the use of commonly used drugs and biologics continues to increase and the resulting burden of disease due to malignancy can be substantial at the population level. However, for most of the proposed pharmacoepidemiological links of cancer, there has been substantial controversy about their validity and often investigations with varying study designs and populations have arrived at different conclusions. For some of these associations, there are already a very large number of studies and even several meta-analyses thereof. However, even meta-analyses on the same topic may reach contradicting results and conclusions.
In this umbrella review, we aimed to collect systematically and critically reassess the results of meta-analyses of common medications that have been associated with increased cancer risk. We aimed to juxtapose the results of meta-analyses on similar drugs and cancer types to see how much they agree or disagree, to understand why disagreements may have arisen, and try to decipher eventually the presence or absence of cancer risks for these pharmacological and biological agents. We examined those associations where there is at least one meta-analysis, including data from randomized trials. For those topics, we evaluated all meta-analyses, regardless of whether they included randomized trials or observational data. We examined in depth those associations where at least one meta-analysis has claimed any nominally statistically significant increased cancer risk. We aimed to see how strong and consistent the evidence was for these claims of significant cancer risks across different types of study designs and different meta-analyses on the same or similar topic.
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