Abstract
BackgroundCardiac 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.MethodsPubMed, 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.ResultsWe 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).ConclusionThe 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.
Highlights
Cancer represents a major health problem facing the world which is responsible for 13% of all deaths worldwide according to the World Health Organization (WHO) [1]
Twenty-four studies reported the association between Cardiac glycosides (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% confidence intervals (CI): 1.247–1.419)
Summary
Cancer represents a major health problem facing the world which is responsible for 13% of all deaths worldwide according to the World Health Organization (WHO) [1]. In 2012, 14.1 million new cancer cases were diagnosed with more than 8 million cancer-specific deaths worldwide [3]. Extensive research has been made to identify the mechanisms of carcinogenicity, most cancers still have poor survival [4]. WHO expects an increase in the number of new cancer cases to 22 million and cancer deaths to 13 million annually over the 2 decades [5]. Extensive research must be done to identify possible risk factors and potential therapeutic agents. 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
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