Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E₂ in Normal Human Colon Tissue

ABSTRACT

Prostaglandin E₂ (PGE₂) in the colon is a pro-inflammatory mediator that is associated with increased risk of colon cancer. In this study, expression of genes in the PGE₂ pathway were quantified in colon biopsies from a trial of a Mediterranean versus a Healthy Eating diet in 113 individuals at high risk for colon cancer. Colon biopsies were obtained before and after 6 months of intervention. Quantitative, real-time PCR was used to measure mRNA expression of prostaglandin H synthases (PTGS1 and 2), prostaglandin E synthases (PTGES1 and 3), prostaglandin dehydrogenase (HPGD), and PGE₂ receptors (PTGER2, PTGER4). The most highly expressed genes were HPGD and PTGS1. In multivariate linear regression models of baseline data, both colon saturated fatty acid concentrations and PTGS1 expression were significant, positive predictors of colon PGE₂ concentrations after controlling for nonsteroidal anti-inflammatory drug use, gender, age, and smoking status. The effects of dietary intervention on gene expression were minimal with small increases in expression noted for PTGES3 in both arms and in PTGER4 in the Mediterranean arm. These results indicate that short-term dietary change had little effect on enzymes in the prostaglandin pathway in the colon and other factors, such as differences in fatty acid metabolism, might be more influential.

Acknowledgments

The authors would like to thank all the individuals who volunteered to participate in the Healthy Eating Study for Colon Cancer Prevention. We would also like to thank Taocong Jin from the Molecular Biology Core Laboratory at the University of Michigan Dental School for assistance with the qrtPCR protocol and analyzing the samples; Dr. Thomas Dafydd and Peter D. Ouillette, both from Department of Pathology, University of Michigan Medical School for assistance with tissue microarray, staining and imaging of the slides. Additionally, we would like to thank the students who assisted with tissue processing: Christine Muller and Phillip Wachowiak. Finally, we would like to thank the coordinator for the study, Mary Rapai, MS and the dietician, Maria Cornellier, RD, MS. This dietary intervention study was registered on the Clinical Trials website, which is maintained by the National Institutes of Health, registration number NCT00475722.

Declaration of interest

None of the authors has conflicts of interest to declare with this reported research.

Funding

The study was supported by NIH grants RO1 CA120381, P50 CA130810 (GI SPORE), Cancer Center Support Grant P30 CA046592, and the Kutsche Family Endowed Chair (Dean Brenner). The study used core resources supported by a Clinical Translational Science Award, NIH grant UL1RR024986 (the Michigan Clinical Research Unit), by the Michigan Diabetes Research Center, NIH grant 5P60 DK20572 (Chemistry Laboratory), and the Michigan Nutrition and Obesity Research Center, NIH grant P30 DK089503.