Efficacy and safety of chemopreventive agents on colorectal cancer incidence and mortality: systematic review and network meta-analysis

Abstract

BackgroundVarious interventions have been tested as primary prevention of colorectal cancers (CRC), but comprehensive evidence comparing them is absent. We examined the effects of various chemopreventive agents (CPAs) on CRC incidence and mortality.MethodsWe did a network meta-analysis based on a systematic review of randomized controlled trials (RCTs) that compared at least one CPA (aspirin, antioxidants, folic acid, vitamin B6, vitamin B12, calcium, vitamin D, alone or in combination) to placebo or other CPA in persons without history of CRC. Several databases were searched from inception up to March 2017. Primary outcomes were early and long-term CRC incidence and mortality.ResultsTwenty-one RCTs comprising 281,063 participants, 9 RCTS comprising 160,101 participants, and 7 RCTs comprising 24,001 participants were included in the network meta-analysis for early risk of CRC incidence, long-term risk of CRC incidence and mortality, respectively. For early CRC incidence, no CPAs were found to be effective. For long-term CRC incidence and mortality, aspirin was the only intervention that showed protective effects with potential dose-dependent effects (risk ratio [RR], 0.74 [95% CI, 0.57–0.97] for high-dose [≥325 mg/day] and RR, 0.81 [95% CI, 0.67–0.98] for very-low-dose [≤100 mg/day]). Similar trend was found for mortality (RR, 0.43 [95% CI, 0.23–0.81] for low-dose [>100–325 mg/day] and RR, 0.65 [95% CI, 0.45–0.94] for very-low-dose). However, in net clinical benefit analysis, when combining risk estimates on mortality from CRC, cardiovascular disease, and pooled risk estimates of major gastrointestinal bleeding, low-dose aspirin provided the highest net survival gain (%) of 1.736 [95% CI, 1.010–2.434].ConclusionAspirin at the dose range of 75–325 mg/day is a safe and effective primary prevention for long-term CRC among people at average risk. None of the other CPAs were found to be effective. There may potentially be differential effects among various doses of aspirin that needs further investigation.

Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women

“…In addition, the detailed NSAID reimbursement data allowed us to consider precise information on NSAID exposure (including molecules, duration, dose, time since last and time since first use). In our cohort, we found that exposure to NSAIDs was associated with a decreased risk of colorectal cancer (HR = 0.67 (0.54–0.82) for ever versus never exposed women; Additional file 1 , Table S5), in close agreement with estimates from meta-analyses [ 52 , 53 ], which provides support for the accuracy of our assessment of NSAID exposure. However, because NSAID is mostly used sporadically (as noted in a study from the French National Health Insurance Claims [ 54 ]), our statistical power remained limited to evaluate the NSAID-breast cancer associations for a long duration of use.…”

Efficacy and safety of celecoxib on the incidence of recurrent colorectal adenomas: a systematic review and meta-analysis

“…Aspirin could potentially alter the risk–benefit balance of celecoxib if used concomitantly. This is due to the fact that aspirin has a modest protective effect on CRC and CV events, yet possesses gastrointestinal toxicity along with major bleedings 10,49,50. As a result, readers should be aware of this limitation.…”

Reduced Plasma Levels of Very-Long-Chain Dicarboxylic Acid 28:4 in Italian and Brazilian Colorectal Cancer Patient Cohorts

“…These data, along with our findings, suggest that VLCDCA 28:4 is maintained at a homeostatic level in the bloodstream and that decrements in the levels of this anti-inflammatory lipid can result in the development of CRC. Inflammation plays an important role in the development of malignancies, such that Inflammatory Bowel Disease (IBD) [14] and Irritable Bowel Syndrome (IBS) [15], are associated with an increased risk of developing CRC, while aspirin [16] and non-aspirin NSAIDs [17] have been shown to decrease the risk of developing CRC. However, the CRC patient population is an heterogeneous group, since CRC can develop via different biochemical pathways.…”