Nonsteroidal anti‐inflammatory drugs but not aspirin are associated with a lower risk of post‐colonoscopy colorectal cancer

Abstract

Background: Although nonsteroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer (CRC) risk, their role in preventing post-colonoscopy CRC (PCCRC) remains undetermined. Aims: To investigate whether NSAIDs reduce PCCRC risk after a negative baseline colonoscopy Methods: This is a retrospective cohort study based on a territory-wide healthcare database of Hong Kong. All patients (aged 40 or above) who underwent colonoscopies between 2005 and 2013 were identified. Exclusion criteria included CRC detected within 6 months of index colonoscopy, prior CRC, inflammatory bowel disease and prior colectomy. The primary outcome was PCCRC-3y diagnosed between 6 and 36 months after index colonoscopy. Sites of CRC were categorised as proximal (proximal to splenic flexure) and distal. The adjusted hazards ratio (aHR) of PCCRC-3y with NSAID and aspirin use (defined as cumulative use for ≥90 days within 5 years before index colonoscopy) was derived by propensity score (PS) regression adjustment of 22 covariates (including patient factors, concurrent medication use and endoscopy centre's performance).Results: Of 187 897 eligible patients, 21 757 (11.6%) were NSAID users. 854 (0.45%) developed PCCRC-3y (proximal cancer: 147 [17.2%]). NSAIDs were associated with a lower PCCRC-3y risk (aHR: 0.54, 95% CI: 0.41-0.70), but not CRC that developed >3 years (aHR: 0.78, 95% CI 0.56-1.09). The aHR was 0.48 (95% CI: 0.24-0.95) for proximal and 0.55 (95% CI: 0.40-0.74) for distal cancer. A duration-and frequency response relationship was observed (P trend < 0.001). For aspirin, the aHR was 1.01 (95% CI: 0.80-1.28). Conclusions:Non-aspirin NSAIDs were associated with lower PCCRC risk after a negative baseline colonoscopy. R E FE R E N C E S

Letter: nonsteroidal anti‐inflammatory drugs reduce the risk of post‐colonoscopy colorectal cancer

“…6 There appears to be an error in the stated adjusted hazard ratio and 95% confidence interval for mefenamic acid, which are presented as 1.27 and 1.77-9.06 (Table 3 of the publication). 1 Fourth, the study did not provide data about adverse effects of NASIDs. NSAIDs can cause gastrointestinal ulcers and/or bleeding, serious cardiovascular events and kidney injury.…”

“…First, NSAID users were older and had a higher proportion of hypertension, diabetes and hyperlipidaemia than non-users ( Table 1 of the publication). 1 This means that NSAID users were more likely to have been taking other drugs such as metformin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. 2,3 In addition, NSAID users often take other drugs for pain control, such as systemic slow-acting drugs.…”

“…5 However, in the study by Cheung et al, the proportion of distal CRCs far exceeded that of proximal (82.8% vs 17.2%). 1 Third, the effects of individual NSAIDs on the 3-year risk of PCCRC were inconsistent. The authors attributed this to the small number of events in NSAID users.…”

A novel plausible mechanism of NSAIDs-induced apoptosis in cancer cells: the implication of proline oxidase and peroxisome proliferator-activated receptor

“…According to these facts, medication with NSAIDs was associated with decreased risk of certain cancer types, particularly gastrointestinal tract cancers (gastric or colorectal cancer), lung, breast, and prostate cancers [10][11][12][13][14]. Clinical and pharmacoepidemiological studies provide evidence that aspirin and other cyclooxygenase-2 enzyme inhibitors lower recurrence of colorectal cancer by about 20% [12,15,16]. Another example is that regular, non-selective COX-2 NSAIDs treatment (i.e.…”

“…All these data suggest COX-independent mechanisms of NSAID-dependent apoptosis in cancer cells. Until now numerous investigations were conducted to confirm that cancer cells treatment with NSAIDs are associated with downregulation of oncogenic factors expression and upregulation of apoptosis pathway with significant role of the PPARγ [12][13][14][15][16]. Since NSAIDs are ligands of PPARγ and PPARγ induces PRODH/POX-dependent apoptosis, this sequence of events may represent the mechanism of anticancer activity of NSAIDs.…”