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Abstract
Oxylipids are potent lipid mediators associated with inflammation-induced colon carcinomas and colon tumor survival. Therefore, oxylipid profiles may be useful as novel biomarkers of colon polyp presence. The aim of this study was to investigate the relationship between plasma non-esterified oxylipids and the presence of colon polyps. A total of 123 Caucasian men, ages 48 to 65, were categorized into three groups: those with no polyps, those with one or more hyperplastic polyps, and those with one or more adenomas. Plasma non-esterified oxylipids were analyzed using solid phase extraction and quantified using a targeted HPLC tandem mass spectrometric analysis. Statistical analyses included Kruskal-Wallis one-way ANOVA with Dunn’s test for multiple comparison and generalized linear models to adjust for confounding factors such as age, anthropometrics, and smoking status. In general, monohydroxy omega-6-derived oxylipids were significantly increased in those with polyps. Concentrations of 5-hydroxyeicosatetraenoic acid (HETE) and 11-HETE were significantly higher in those with hyperplastic polyps and adenomas compared to those with no polyps. Arachidonic acid-derived HETEs were significantly associated with colon polyp types, even after adjusting for age, smoking, and body mass index or waist circumference in regression models. Since many of these oxylipids are formed through oxygenation by lipoxygenases (i.e., 5-, 12-, and 15-HETE, and 15- hydroxyeicosatrienoic acid [HETrE]) or auto-oxidative reactions (i.e., 11-HETE), this may indicate that lipoxygenase activity and lipid peroxidation are increased in those with colon polyps. In addition, since oxylipids such as 5-, 12-, and 15-HETE are signaling molecules involved in inflammation regulation, these oxylipids may have important functions in inflammation-associated polyp presence. Future studies should be performed in a larger cohorts to investigate if these oxylipids are useful as potential biomarkers of colon polyps.
Highlights
Colon polyps are formed by abnormal growth of tissue on the lining of the colon[1]
Western diets are typically high in n-6 polyunsaturated fatty acids (PUFAs) such as linoleic acid (LA), which can alter the ratio of PUFAs leading to a shift towards n-6 fatty acid elongation and desaturation, resulting in accumulation of arachidonic acid (ARA) and ARA-derived oxylipids
body mass index (BMI), waist circumference (WC), smoking status, and non-esterified PUFA and plasma oxylipid concentrations for the overall population (n = 123) are separated into three groups based on the polyp type (Table 1)
Summary
Colon polyps are formed by abnormal growth of tissue on the lining of the colon[1]. Polyps can be categorized based on number, size, and histologic characteristics, such as hyperplastic polyps or adenomas. Since age is a risk factor associated with colorectal cancer, it is recommended that all adults in the United States have regular examinations by age 50. Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are structurally similar oxylipid substrates, and accumulation of one PUFA family can lead to enzymatic competition and alter downstream lipid metabolism. Previous studies investigated PUFA dietary intake effects on adenomas and colon cancer risk, the results from these studies are mixed[17,18,19]. 63 plasma oxylipids were quantified to determine oxylipid classes and concentrations significantly associated with colon polyp presence and type in 123 males. After false discovery correction and across all statistical analyses, the plasma ARA-derived oxylipids 5- and 11-hydroxyeciosatetreanoic acid (HETEs) were significantly elevated and associated with polyp type. Concentration ranges of these HETEs were associated with an increased likelihood of polyp presence
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