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Aspirin and colorectal cancer: the promise of precision chemoprevention

Abstract

Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action.

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Figure 1: Timeline of notable human studies in aspirin chemoprevention.
Figure 2: The hypothesized inter-related mechanisms of aspirin chemoprevention.

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Correspondence to Andrew T. Chan.

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Competing interests

A.T.C. has previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pfizer Inc. and Pozen Inc. This study was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Pfizer Inc. or Pozen Inc. D.A.D. and Y.C. declare no competing interests.

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Glossary

Case–control studies

A type of observational study design in which two groups differ according to outcome (for example, in which those with the disease or condition (cases) are compared with disease-free individuals (controls)). These studies can be nested within a larger cohort with only a subset of the larger control population being used.

Confidence interval

(CI). A measure of the uncertainty associated with a sample estimate for a given parameter.

Events per 1,000 person-years

Also known as the incidence density rate or person–time incidence rate. This approach normalizes event observations to the amount of observation time and is useful if observation times are not constant across a sample population or the risk of an event varies over time.

Fractal dimension

(FRAC). A spectroscopic measure of light scattering due to nanoscale architectural changes in mass density of cellular components that has been associated with early neoplastic changes in epithelial cells.

Glucuronidation

The addition of glucuronic acid to a substrate.

H2 blocker

A drug that inhibits the production of gastric acid by targeting histamine H2 receptors of gastric parietal cells.

Hazard ratio

(HR). A measure of the ratio of the hazard rates (the rate at which an event occurs) for a given outcome (for example, cancer) described by an explanatory variable (for example, aspirin versus placebo).

Incidence rate ratio

(IRR). A measure of the ratio between the rates of how often an outcome (for example, cancer) occurs in a population at any given time according to an explanatory variable (for example, aspirin versus placebo).

Odds ratio

(OR). A measure of association representing the odds (the probability of disease divided by 1 minus the probability) of an outcome according to an explanatory variable (for example, aspirin users versus non-users).

P heterogeneity

A statistic that measures the significance of the difference (or heterogeneity) between two effect sizes.

P interaction

A statistic that measures the significance of the effect of a given exposure or explanatory variable on a second exposure or explanatory variable, and vice versa.

Proton pump inhibitor

A drug that inhibits the production of gastric acid by targeting the proton pump transport activity of gastric parietal cells. Proton pump inhibitors are generally more effective than H2 blockers.

P trend

A statistic that measures the significance of a correlation of effect size, either positive or negative, across a continuous or ordinal variable.

Relative risk

(RR). The probability of an outcome (for example, cancer) occurring in one group (for example, aspirin) versus the probability in a comparison group (for example, placebo).

Serrated carcinogenesis pathway

A carcinogenesis pathway in which colorectal tumours are characterized by epigenetic dysregulation (promoter hypermethylation), BRAF mutation and activation, and often microsatellite instability, rather than adenomatous polyposis coli (APC) mutations and chromosomal instability.

Single nucleotide polymorphism

(SNP). A common type of genetic variation in which a single nucleotide or base occurs at a specific position in the genome that is different from the expected or reference nucleotide.

Spectral slope

(SPEC). A spectroscopic measure of light scattering due to nanoscale architectural changes in the size distribution of cellular components that has been associated with early neoplastic changes in epithelial cells.

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Drew, D., Cao, Y. & Chan, A. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer 16, 173–186 (2016). https://doi.org/10.1038/nrc.2016.4

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