Abstract

The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome.

Highlights

  • Western diets with low fiber consumption are a risk factor for colorectal cancer (CRC)[1]

  • Low serum abundance of both the glucuronide and sulfate conjugated forms were associated with tumor localization, namely colon compared to the rectum (P = 0.049 and P = 0.012, respectively)

  • Tumor differentiation was associated with serum enterolactone levels: the CRC patients with low-grade tumors had higher enterolactone levels than the patients with poorly differentiated tumors

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Summary

Introduction

Western diets with low fiber consumption are a risk factor for colorectal cancer (CRC)[1]. Plant lignans are metabolized by multistep processes, catalyzed by intestinal bacteria including Moryella, Streptobacillus, Fastidiosipila and Acetanaerobacterium, resulting in the production of enterolignans, enterodiol and enterolactone. Enterolactone has a similar structure to 17B-estradiol and is capable of binding to estrogen receptors[4,5]. This may explain the reported association between enterolactone and decreased risk of hormone-sensitive cancers[6]. No correlation was observed in the EPIC-Norfolk study between phytoestrogen exposure and the risk of colorectal cancer risk in an European population[14], whereas another study from the same population found an association between enterolactone and CRC risk among women based on a comprehensive phytoestrogen nutrient intake database[15]. Despite its potential tumor-inhibiting effects, the alterations in preoperative serum enterolactone levels in CRC patients and their clinical significance have not been well-defined

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