Association between anthraquinone laxatives and colorectal cancer: protocol for a systematic review and meta-analysis

Introduction: Anthraquinones (AQs) are found in rhubarb root, senna leaf and pod, cascara, buckhorn, and aloe. AQs have several biological effects and adverse events related to their use have been reported. AQs containing products have mainly been used for their laxative properties and in short-term therapy. AQ laxatives should not be used continuously for periods exceeding 1–2 weeks. In fact, there have historically been some concerns about the long-term use of AQs. In particular, in the past their chronic use was associated with an increased risk of colorectal cancer (CRC). As no firm evidence exists to the potential association between the chronic use of oral AQs and the risk of CRC, we aimed to quantify this risk performing a systematic review and meta-analysis. Methods and analysis: We will search MEDLINE, Embase, Scopus, the Cochrane Library, Google Scholar and Clinicaltrials.gov for clinical trials and observational studies performed on subjects taking AQs and assessing incident CRC as outcome were selected. To avoid missing any relevant studies, we will search the bibliographies of retrieved papers and recent reviews in the field. Experimental interventions will include products containing oral AQ laxatives, in particular AQs derived from rhubarb, senna, cascara, buckhorn, and aloe. Two review authors will independently screen title, abstract and full texts, and will independently extract data from included studies. Primary outcome include safety with regards to CRC. Secondary safety outcome will include “melanosis coli”. We will also consider all other adverse events reported in the included studies, in particular: intestinal bleeding, alterations of gastrointestinal motility, and potential for dependence. Where possible and appropriate, for each outcome a meta-analysis will be performed using a random-effects model within a frequentist framework. Ethics and dissemination: Results will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.