Systematic review: interactions between aspirin, and other nonsteroidal anti‐inflammatory drugs, and polymorphisms in relation to colorectal cancer

Abstract

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin (acetylsalicylic acid, ASA). Long-term use of NSAIDs has been associated with lowered risk of colorectal cancer (CRC), but the use is hampered by adverse effects. Also, the anti-carcinogenic effects of NSAIDs are incompletely understood. Understanding biological effects of NSAIDs may help developing new preventive medical strategies.AimTo identify gene–environment interactions between genetic variation and NSAID use in relation to risk of CRC.MethodsWe performed a PubMed literature search and all studies reporting original data on interactions between NSAIDs and polymorphisms in relation to CRC were evaluated.ResultsWe found indications that aspirin interacted with rs6983267 close to MYC (encoding a transcription factor involved in cell cycle progression, apoptosis and cellular transformation) and NSAIDs interacted with rs3024505 and rs1800872 in or close to IL10 (encoding IL-10) in preventing CRC. Homozygous carriers of the variant allele of rs6983267 (ca. 25% of the population) halved their risk for CRC by aspirin use compared to homozygous wildtype carriers who did not benefit from aspirin intake. No interaction between use of NSAIDs and PTGS-2 (encoding COX-2) in relation to CRC risk was detected. Other findings of interactions between genes in inflammatory and oncogenic pathways and NSAIDs were considered suggestive.ConclusionsKnowledge of underlying biological effects of NSAIDs in relation to CRC is scarce and the basis for stratifying the patients for preventive treatment is not yet available. Further studies assessing interactions between long-term NSAID exposure and genetic variation in relation to CRC are warranted in large well-characterised prospective cohorts.

Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study

“…Gene-environment interaction analyses may identify underlying biological pathways associated with effects of diet (46,47). Our analyses suggest that the meat carcinogenic pathway involves activation of TLR1 and TLR10 followed by activation of NF-ĸB-initiated transcription of inflammatory genes (Figure 1).…”

Association between aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism and susceptibility to colorectal cancer: a meta-analysis

“…There has been an increase in the incidence of CRC over the past few years due to demographical changes and the implementation of a Western lifestyle in developing countries (Andersen and Vogel, 2014). It is a multifactorial disease resulting from complex interactions between genetic, epigenetic, and environmental factors.…”

Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats

“…DMH is metabolized in the liver to form azoxymethane and methylazoxymethanol which is further transported to the colon via bile or blood to generate its ultimate carcinogenic metabolite, diazonium ion, which elicits an oxidative stress by methylating biomolecules of colonic epithelial cells and leads to promutagenic events as a result of inflammation and tumor promotion. It is already reported that the overexpression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) is associated with colorectal cancer [11].…”

“…Aspirin or acetylsalicylic acid is a drug in the salicylate family and of the class of NSAID. The epidemiological studies and clinical trials indicate that longterm use of Aspirin could possibly decrease the incidence of certain malignancies, including colorectal, oesophageal, breast, lung and bladder cancer [11][12][13]. However, long-term use of Aspirin is limited to gastric and renal toxicity [14].…”