Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.

<h4>Background</h4>Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerni...

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Main Authors: Mohamed Hosny Osman, Eman Farrag, Mai Selim, Mohamed Samy Osman, Arwa Hasanine, Azza Selim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0178611
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author Mohamed Hosny Osman
Eman Farrag
Mai Selim
Mohamed Samy Osman
Arwa Hasanine
Azza Selim
author_facet Mohamed Hosny Osman
Eman Farrag
Mai Selim
Mohamed Samy Osman
Arwa Hasanine
Azza Selim
author_sort Mohamed Hosny Osman
collection DOAJ
description <h4>Background</h4>Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerning the association between CGs use and cancer risk yielded inconsistent results. We have performed a systematic review and meta-analysis to summarize the effects of CGs on cancer risk and mortality.<h4>Methods</h4>PubMed, Scopus, Cochrane library, Medline and Web of Knowledge were searched for identifying relevant studies. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects model.<h4>Results</h4>We included 14 case-control studies and 15 cohort studies published between 1976 and 2016 including 13 cancer types. Twenty-four studies reported the association between CGs and cancer risk and six reported the association between CGs and mortality of cancer patients. Using CGs was associated with a higher risk of breast cancer (RR = 1.330, 95% CI: 1.247-1.419). Subgroup analysis showed that using CGs increased the risk of ER+ve breast cancer but not ER-ve. Using CGs wasn't associated with prostate cancer risk (RR = 1.015, 95% CI: 0.868-1.87). However, CGs decreased the risk in long term users and showed a protective role in decreasing the risk of advanced stages. CGs use was associated with increased all-cause mortality (HR = 1.35, 95% CI: 1.248-1.46) but not cancer-specific mortality (HR = 1.075, 95% CI: 0.968-1.194).<h4>Conclusion</h4>The anti-tumor activity of CGs observed in pre-clinical studies requires high concentrations which can't be normally tolerated in humans. However, the estrogen-like activity of CGs could be responsible for increasing the risk of certain types of tumors.
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spelling doaj-art-c1f5f983c71d4b4c92ac600fcc36c9c52025-08-20T03:32:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017861110.1371/journal.pone.0178611Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.Mohamed Hosny OsmanEman FarragMai SelimMohamed Samy OsmanArwa HasanineAzza Selim<h4>Background</h4>Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerning the association between CGs use and cancer risk yielded inconsistent results. We have performed a systematic review and meta-analysis to summarize the effects of CGs on cancer risk and mortality.<h4>Methods</h4>PubMed, Scopus, Cochrane library, Medline and Web of Knowledge were searched for identifying relevant studies. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects model.<h4>Results</h4>We included 14 case-control studies and 15 cohort studies published between 1976 and 2016 including 13 cancer types. Twenty-four studies reported the association between CGs and cancer risk and six reported the association between CGs and mortality of cancer patients. Using CGs was associated with a higher risk of breast cancer (RR = 1.330, 95% CI: 1.247-1.419). Subgroup analysis showed that using CGs increased the risk of ER+ve breast cancer but not ER-ve. Using CGs wasn't associated with prostate cancer risk (RR = 1.015, 95% CI: 0.868-1.87). However, CGs decreased the risk in long term users and showed a protective role in decreasing the risk of advanced stages. CGs use was associated with increased all-cause mortality (HR = 1.35, 95% CI: 1.248-1.46) but not cancer-specific mortality (HR = 1.075, 95% CI: 0.968-1.194).<h4>Conclusion</h4>The anti-tumor activity of CGs observed in pre-clinical studies requires high concentrations which can't be normally tolerated in humans. However, the estrogen-like activity of CGs could be responsible for increasing the risk of certain types of tumors.https://doi.org/10.1371/journal.pone.0178611
spellingShingle Mohamed Hosny Osman
Eman Farrag
Mai Selim
Mohamed Samy Osman
Arwa Hasanine
Azza Selim
Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
PLoS ONE
title Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
title_full Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
title_fullStr Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
title_full_unstemmed Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
title_short Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.
title_sort cardiac glycosides use and the risk and mortality of cancer systematic review and meta analysis of observational studies
url https://doi.org/10.1371/journal.pone.0178611
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