15-PGDH Expression in Normal Mucosa May Be Biomarker for Aspirin Prevention of Colorectal Cancer

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Aspirin use reduces the risk of colorectal cancer at least in part via inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, COX-2) pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide; 15-PGDH, HPGD) is a metabolic antagonist of PTGS2 and is downregulated in colorectal cancer.

In a study reported in Science Translational Medicine, Fink and colleagues investigated whether the effect of aspirin in reducing risk of colorectal cancer is antagonized by low 15-PGDH expression in normal colon mucosa. The study involved analysis of data on aspirin use collected every 2 years and occurrence of colorectal cancer among 127,865 participants in the Nurses’ Health Study and the Health Professionals Follow-Up Study.

A total of 270 colorectal cancer cases in which 15-PGDH expression could be assessed were identified. Compared with nonuse, regular aspirin use was associated with lower risk of development of colorectal cancer in normal colonic mucosa with high 15-PGDH expression (multivariate hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.34–0.71) but not in normal colonic mucosa with low 15-PGDH expression (multivariate HR = 0.90, 95% CI = 0.63–1.27, P = .018 for heterogeneity).

The investigators concluded, “Regular aspirin use was associated with lower incidence of colorectal cancers arising in association with high 15-PGDH expression, but not with low 15-PGDH expression in normal colon mucosa. This suggests that 15-PGDH expression level in normal colon mucosa may serve as a biomarker that may predict stronger benefit from aspirin chemoprevention.” ■

Fink SP, et al: Sci Transl Med 6:233re2, 2014.