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Special Issue "Nutrition and Colorectal Cancer"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (1 December 2018)

Special Issue Editor

Guest Editor
Dr. Nitin Shivappa

Univ South Carolina, Canc Prevent & Control Program, Columbia, SC 29208, USA
Website | E-Mail
Interests: diet; inflammation; colorectal cancer; dietary assessment

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the third most common form of cancer worldwide and is one of the leading causes of cancer-related deaths. Incidence and mortality rates of CRC vary widely with higher incidence rates in developed nations and lower incidence rates in Asia, Africa, and most Latin American countries. Research suggests various dietary components to have an involvement in the development of CRC but the results have been inconsistent. The 2012 American Institute for Cancer Research/World Cancer Research Fund Continuous Update Project (CUP) reported that consumption of red and processed meat, which are pro-inflammatory, is associated with an increased risk of CRC. Conversely, the consumption of dietary fiber, which is anti-inflammatory, is inversely associated with risk of CRC. Furthermore, other dietary components, such as tea and coffee, which we have found to be anti-inflammatory, have demonstrated various health benefits, including lower cancer incidence and mortality. This Special Issue of Nutrients, entitled “Nutrition and Colorectal Cancer”, welcomes the submission of manuscripts either describing original research or reviewing the scientific literature on this topic.

Topics must have a clear focus on the relationship between whole diet described through dietary patterns, dietary indices and CRC risk, and mortality. We welcome papers from different regions of the world. Research strategies should help in developing a stronger understanding of nutritional approaches for either preventing or managing CRC.

Dr. Nitin Shivappa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dietary patterns
  • colorectal cancer
  • dietary indices
  • mortality

Published Papers (8 papers)

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Research

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Open AccessArticle
Dietary Inflammatory Index and Odds of Colorectal Cancer and Colorectal Adenomatous Polyps in a Case-Control Study from Iran
Nutrients 2019, 11(6), 1213; https://doi.org/10.3390/nu11061213
Received: 29 March 2019 / Revised: 22 May 2019 / Accepted: 24 May 2019 / Published: 28 May 2019
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Abstract
Background: Chronic inflammation is implicated in the development of colorectal cancer (CRC) and its precursor; colorectal adenomatous polyps (CAP). Some dietary factors are important triggers for systemic inflammation. Therefore, the present study aimed to investigate the association between the dietary inflammatory index (DII [...] Read more.
Background: Chronic inflammation is implicated in the development of colorectal cancer (CRC) and its precursor; colorectal adenomatous polyps (CAP). Some dietary factors are important triggers for systemic inflammation. Therefore, the present study aimed to investigate the association between the dietary inflammatory index (DII®) and the risk of CRC and CAP in an Iranian case-control study. Methods: 134 newly diagnosed CRC patients, 130 newly diagnosed CAP patients, and 240 hospitalized controls were recruited using convenience sampling. Energy-adjusted DII (E-DII) scores were computed based on dietary intake assessed using a reproducible and valid 148-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) after adjusting for confounders. Results: The E-DII score ranged between −4.23 (the most anti-inflammatory score) to +3.89 (the most pro-inflammatory score). The multivariable-adjusted ORs for participants in the 3rd tertile compared to the 1st tertile was 5.08 (95%CI: 2.70–9.56; P-trend < 0.0001) for CRC and 2.33 (95% CI: 1.30–4.02; P-trend = 0.005) for CAP. Conclusions: Our findings suggest that more pro-inflammatory diets, indicated by higher E-DII scores, might increase the risk of both CRC and CAP. Future steps should include testing these associations in a prospective setting in Iran. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Open AccessFeature PaperArticle
Polymethoxylated Flavones Target Cancer Stemness and Improve the Antiproliferative Effect of 5-Fluorouracil in a 3D Cell Model of Colorectal Cancer
Nutrients 2019, 11(2), 326; https://doi.org/10.3390/nu11020326
Received: 4 January 2019 / Revised: 26 January 2019 / Accepted: 30 January 2019 / Published: 2 February 2019
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Abstract
Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, [...] Read more.
Polymethoxylated flavones (PMFs) from citrus fruits are reported to present anticancer potential. However, there is a lack of information regarding their effect on cancer stem cell (CSC) populations, which has been recognized as responsible for tumor initiation, relapse, and chemoresistance. In this study, we evaluated the effect of an orange peel extract (OPE) and its main PMFs, namely, nobiletin, sinensetin, tangeretin, and scutellarein tetramethylether in targeting cell proliferation and stemness using a 3D cell model of colorectal cancer composed of HT29 cell spheroids cultured for 7 days in stirred conditions. Soft agar assay, ALDH1 activity, and relative quantitative gene expression analysis of specific biomarkers were carried out to characterize the stemness, self-renewal, and mesenchymal features of HT29 cell spheroids. Then, the impact of OPE and PMFs in reducing cell proliferation and modulating cancer stemness and self-renewal was assessed. Results showed that, when compared with monolayer cultures, HT29 cell spheroids presented higher ALDH1 activity (81.97% ± 5.27% compared to 63.55% ± 17.49% for 2D), upregulation of CD44, PROM1, SOX9, and SNAI1 genes (1.83 ± 0.34, 2.54 ± 0.51, 2.03 ± 0.15, and 6.12 ± 1.59 times) and high self-renewal capability (352 ± 55 colonies compared to 253 ± 42 for 2D). Incubation with OPE (1 mg/mL) significantly inhibited cell proliferation and modulated cancer stemness and self-renewal ability: colony formation, ALDH1 activity, and the expression of cancer stemness biomarkers PROM1 and LGR5 were significantly reduced (0.66 ± 0.15 and 0.51 ± 0.14 times, respectively). Among all PMFs, tangeretin was the most efficient in targeting the CSC population by decreasing colony formation and the expression of PROM1 and LGR5. Scutellarein tetramethylether was shown to modulate markers of mesenchymal/metastatic transition (increasing CDH1 and reducing ZEB1 and SNAI1) and nobiletin was capable of downregulating PROM1 and SNAI1 expression. Importantly, all PMFs and OPE were shown to synergistically interact with 5-fluorouracil, improving the antiproliferative response of this drug. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Open AccessArticle
n-6 Linoleic Acid Induces Epigenetics Alterations Associated with Colonic Inflammation and Cancer
Nutrients 2019, 11(1), 171; https://doi.org/10.3390/nu11010171
Received: 2 December 2018 / Revised: 3 January 2019 / Accepted: 10 January 2019 / Published: 15 January 2019
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Abstract
The farnesoid-X-receptor (FXR) protects against inflammation and cancer of the colon through maintenance of intestinal bile acid (BA) homeostasis. Conversely, higher levels of BA and cyclooxygenase-2 (COX-2) are risk factors for inflammation and cancer of the colon. In the United States, n-6 [...] Read more.
The farnesoid-X-receptor (FXR) protects against inflammation and cancer of the colon through maintenance of intestinal bile acid (BA) homeostasis. Conversely, higher levels of BA and cyclooxygenase-2 (COX-2) are risk factors for inflammation and cancer of the colon. In the United States, n-6 linoleic acid (LA) is the most commonly used dietary vegetable fat. Metabolism of n-6 fatty acids has been linked to a higher risk of intestinal cancer. The objectives of this study were to investigate in colonic mucosa the effects of a high-fat diet rich in LA (n-6HFD) on CpG methylation of Fxr and prostaglandin-endoperoxide synthase-2 (Ptsg-2) genes, and the impact on the expression of tumor suppressor adenomatous polyposis Coli (Apc) and proliferative cyclin D1 (Ccnd1) genes. Weaned C57BL/6J male mice were fed for 6 weeks either an n-6HFD containing 44% energy (44%E) from 22% safflower oil (SO, 76% LA by weight) or a 13% energy (13%E) control diet (Control) from SO (5% by weight). Mice fed the n-6HFD had reduced (60%) Fxr promoter CpG methylation and increased (~50%) Fxr mRNA. The expression of FXR-target ileal bile acid-binding protein (Ibabp), small heterodimer protein (Shp), and anti-inflammatory peroxisome proliferator-activated-γ1 genes was increased. The n-6HFD reduced Ptgs-2 CpG methylation, increased the expression of Cox-2, and increased Apc CpG methylation in colonic mucosa. Accordingly, reduced expression of Apc was coupled to accumulation of c-JUN and Ccnd1, respectively cofactor and gene targets for the β-catenin/Wnt signaling pathway. Finally, the n-6HFD reduced the expression of histone deacetylase-1 while favoring the accumulation of acetylated histone 3. We conclude that an n-6HFD epigenetically modifies Fxr, leading to the activation of downstream factors that participate in BA homeostasis. However, epigenetic activation of Ptsg-2 coupled with silencing of Apc and accumulation of C-JUN and Ccnd1 may increase the risk of inflammation and cancer of the colon. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Open AccessArticle
Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?
Nutrients 2019, 11(1), 110; https://doi.org/10.3390/nu11010110
Received: 27 November 2018 / Revised: 27 December 2018 / Accepted: 3 January 2019 / Published: 8 January 2019
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Abstract
Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. [...] Read more.
Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Open AccessArticle
Cordyceps militaris Grown on Germinated Soybean Suppresses KRAS-Driven Colorectal Cancer by Inhibiting the RAS/ERK Pathway
Nutrients 2019, 11(1), 20; https://doi.org/10.3390/nu11010020
Received: 10 December 2018 / Accepted: 19 December 2018 / Published: 21 December 2018
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Abstract
Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven [...] Read more.
Cordyceps militaris is a commonly used medicinal mushroom containing various therapeutic effects such as anti-inflammatory, anti-allergic, and anti-cancer activities. This study examined whether Cordyceps militaris on germinated soybeans (GSC) has a suppressive effect on a v-ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer which is notorious for its un-druggable features and the ineffectiveness of conventional therapies against it. GSC extract was prepared and its proximate composition and amino acids were analyzed. The suppressive effects were investigated with the KRAS-driven colorectal cancer cell-line, SW480. SW480 proliferation, clonogenic potential, apoptosis, and the RAS/extracellular signal-regulated kinase (ERK) pathway under the GSC treatment were analyzed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, flow cytometry, and Western blot, respectively. An in vivo experiment with the SW480 xenograft mouse model was performed. As a result, GSC suppressed cell proliferation by inducing the apoptosis of KRAS-driven colorectal cancer cells and inhibited clonogenic capabilities. The decrease of KRAS and ERK phosphorylation was detected by Western blot. Tumor growth was significantly suppressed when GSC was introduced to the tumor-xenograft mouse model. In conclusion, GSC suppressed KRAS-driven colorectal cancer growth both in vitro and in vivo, and can be used as an alternative or simultaneous approach in colorectal cancer therapy. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Open AccessArticle
Dose-Response Relationship between Serum Retinol Levels and Survival in Patients with Colorectal Cancer: Results from the DACHS Study
Nutrients 2018, 10(4), 510; https://doi.org/10.3390/nu10040510
Received: 24 March 2018 / Revised: 6 April 2018 / Accepted: 13 April 2018 / Published: 19 April 2018
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Abstract
Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were [...] Read more.
Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were determined in serum collected shortly after diagnosis by mass spectrometry. Associations between serum retinol levels and survival outcomes were assessed using multivariable Cox regression and dose-response analyses. The joint association of serum retinol and serum 25-hydroxyvitamin D3 (25(OH)D3) with survival outcomes was also examined. During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Dose-response curves showed an inverse relationship between serum retinol levels and survival endpoints in the range of <2.4 µmol/L, but no associations at higher levels. Low (<1.2 µmol/L) versus high (≥2.4 µmol/L) serum retinol levels were associated with poorer overall survival (Hazard ratio (HR) = 1.46, 95% confidence interval (CI) = 1.19–1.78, P-trend = 0.0003) and CRC-specific survival (HR = 1.69, 95% CI = 1.33–2.15, P-trend < 0.0001). Joint presence of low serum retinol (<1.2 µmol/L) and low 25(OH)D3 (<30 nmol/L) was associated with a particularly strong decrease in overall and CRC-specific survival. Low serum retinol levels were identified as a predictor of poor survival in CRC patients, in particular when co-occurring with low serum concentrations of 25(OH)D3. The clinical implications of these findings require further investigation. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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Review

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Open AccessReview
Colorectal Cancer and Nutrition
Nutrients 2019, 11(1), 164; https://doi.org/10.3390/nu11010164
Received: 27 November 2018 / Revised: 10 January 2019 / Accepted: 10 January 2019 / Published: 14 January 2019
Cited by 2 | PDF Full-text (212 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon [...] Read more.
Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
Open AccessReview
Olive Oil Effects on Colorectal Cancer
Nutrients 2019, 11(1), 32; https://doi.org/10.3390/nu11010032
Received: 28 November 2018 / Revised: 11 December 2018 / Accepted: 15 December 2018 / Published: 23 December 2018
Cited by 2 | PDF Full-text (1985 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer is the fourth cause of cancer-related death worldwide. A Mediterranean diet showed protective action against colorectal cancer due to the intake of different substances. Olive oil is a fundamental component of the Mediterranean diet. Olive oil is rich in high-value health [...] Read more.
Colorectal cancer is the fourth cause of cancer-related death worldwide. A Mediterranean diet showed protective action against colorectal cancer due to the intake of different substances. Olive oil is a fundamental component of the Mediterranean diet. Olive oil is rich in high-value health compounds (such as monounsaturated free fatty acids, squalene, phytosterols, and phenols). Phenolic compounds exert favourable effects on free radicals, inflammation, gut microbiota, and carcinogenesis. The interaction between gut microbiota and olive oil consumption could modulate colonic microbial composition or activity, with a possible role in cancer prevention. Gut microbiota is able to degrade some substances found in olive oil, producing active metabolites with chemopreventive action. Further clinical research is needed to clarify the beneficial effects of olive oil and its components. A better knowledge of the compounds found in olive oil could lead to the development of nutritional supplements or chemotherapeutic agents with a potential in the prevention and treatment of colorectal cancer. Full article
(This article belongs to the Special Issue Nutrition and Colorectal Cancer)
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