title: 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.
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.|b Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.|c Department of Nutrition , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
authors.forename: ElKhansa
authors.initials: E
authors.lastname: Sidahmed
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.|d Department of Biostatistics , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Ananda
authors.initials: A
authors.lastname: Sen
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ren
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Arsh
authors.initials: A
authors.lastname: Patel
authors.affiliation: e Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA.
authors.forename: D Kim
authors.initials: DK
authors.lastname: Turgeon
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Mack T
authors.initials: MT
authors.lastname: Ruffin
authors.affiliation: e Department of Internal Medicine , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.affiliation: a Department of Family Medicine , University of Michigan , Ann Arbor , MI , USA.|b Department of Environmental Health Sciences , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Zora
authors.initials: Z
authors.lastname: Djuric
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003106:Colon / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D000072001:Diet, Healthy; D038441:Diet, Mediterranean; D015232:Dinoprostone / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008824:Michigan / Q000453:epidemiology; D008875:Middle Aged; D000071876:Prostaglandin-E Synthases / Q000235:genetics / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone