TLR4 and NOD2/CARD15 Polymorphisms and Their Association with Dietary Factors in Colorectal Cancer

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ( 219 ), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.

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Dietary factors and polymorphisms in vitamin D metabolism genes: the risk and prognosis of colorectal cancer in northeast China

Scientific Reports ◽

10.1038/s41598-017-09356-1 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 9

Author(s):

Chen Gong ◽

Zhiping Long ◽

Yanming Yu ◽

Lin Zhu ◽

Jingshen Tian ◽

...

Keyword(s):

Colorectal Cancer ◽

Vitamin D ◽

Northeast China ◽

Dietary Factors ◽

Vitamin D Metabolism

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The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

Frontiers in Oncology ◽

10.3389/fonc.2020.583372 ◽

2020 ◽

Vol 10 ◽

Author(s):

Bene A. Ekine-Afolabi ◽

Anoka A. Njan ◽

Solomon O. Rotimi ◽

Anu R. I. ◽

Attia M. Elbehi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Dna Methyltransferase ◽

Molecular Mechanisms ◽

Cell Communication ◽

Extracellular Vesicle ◽

Dietary Factors ◽

Tumor Onset ◽

Non Coding Rnas ◽

The Impact

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

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Targeting Altered Energy Metabolism in Colorectal Cancer: Oncogenic Reprogramming, the Central Role of the TCA Cycle and Therapeutic Opportunities

Cancers ◽

10.3390/cancers12071731 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1731 ◽

Cited By ~ 1

Author(s):

Carina Neitzel ◽

Philipp Demuth ◽

Simon Wittmann ◽

Jörg Fahrer

Keyword(s):

Colorectal Cancer ◽

Energy Metabolism ◽

Pyruvate Dehydrogenase ◽

Pyruvate Dehydrogenase Complex ◽

Tca Cycle ◽

Dietary Factors ◽

Pyruvate Dehydrogenase Kinase ◽

Driver Mutations ◽

The Tca Cycle

Colorectal cancer (CRC) is among the most frequent cancer entities worldwide. Multiple factors are causally associated with CRC development, such as genetic and epigenetic alterations, inflammatory bowel disease, lifestyle and dietary factors. During malignant transformation, the cellular energy metabolism is reprogrammed in order to promote cancer cell growth and proliferation. In this review, we first describe the main alterations of the energy metabolism found in CRC, revealing the critical impact of oncogenic signaling and driver mutations in key metabolic enzymes. Then, the central role of mitochondria and the tricarboxylic acid (TCA) cycle in this process is highlighted, also considering the metabolic crosstalk between tumor and stromal cells in the tumor microenvironment. The identified cancer-specific metabolic transformations provided new therapeutic targets for the development of small molecule inhibitors. Promising agents are in clinical trials and are directed against enzymes of the TCA cycle, including isocitrate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase complex (PDC) and α-ketoglutarate dehydrogenase (KGDH). Finally, we focus on the α-lipoic acid derivative CPI-613, an inhibitor of both PDC and KGDH, and delineate its anti-tumor effects for targeted therapy.

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Recent advances in clinical practice: colorectal cancer chemoprevention in the average-risk population

Gut ◽

10.1136/gutjnl-2020-320990 ◽

2020 ◽

Vol 69 (12) ◽

pp. 2244-2255 ◽

Cited By ~ 2

Author(s):

Nicolas Chapelle ◽

Myriam Martel ◽

Esther Toes-Zoutendijk ◽

Alan N Barkun ◽

Marc Bardou

Keyword(s):

Colorectal Cancer ◽

Fruits And Vegetables ◽

Healthy Lifestyle ◽

Mortality Rates ◽

Preliminary Evidence ◽

Dietary Factors ◽

Normal Colonic Mucosa ◽

Average Risk ◽

Level Of Evidence ◽

Incidence And Mortality

Colorectal cancer (CRC) is one of the most common and lethal malignancies in Western countries. Its development is a multistep process that spans more than 15 years, thereby providing an opportunity for prevention and early detection. The high incidence and mortality rates emphasise the need for prevention and screening. Many countries have therefore introduced CRC screening programmes. It is expected, and preliminary evidence in some countries suggests, that this screening effort will decrease CRC-related mortality rates. CRC prevention involves a healthy lifestyle and chemoprevention—more specifically, oral chemoprevention that can interfere with progression from a normal colonic mucosa to adenocarcinoma. This preventive effect is important for individuals with a genetic predisposition, but also in the general population. The ideal chemopreventive agent, or combination of agents, remains unknown, especially when considering safety during long-term use. This review evaluates the evidence across 80 meta-analyses of interventional and observational studies of CRC prevention using medications, vitamins, supplements and dietary factors. This review suggests that the following factors are associated with a decreased incidence of CRC: aspirin, non-steroidal anti-inflammatory drugs, magnesium, folate, a high consumption of fruits and vegetables, fibre and dairy products. An increased incidence of CRC was observed with frequent alcohol or meat consumption. No evidence of a protective effect for tea, coffee, garlic, fish and soy products was found. The level of evidence is moderate for aspirin, β-carotene and selenium, but is low or very low for all other exposures or interventions.

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Prevention of Colorectal Neoplasia

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0036-1584086 ◽

2016 ◽

Vol 29 (04) ◽

pp. 353-362 ◽

Cited By ~ 2

Author(s):

Scott Dolejs ◽

Benjamin Gayed ◽

Alyssa Fajardo

Keyword(s):

Physical Activity ◽

Colorectal Cancer ◽

Vitamin D ◽

Colorectal Neoplasia ◽

The United States ◽

Lifestyle Changes ◽

Dietary Factors ◽

Chemopreventive Agents ◽

Incidence And Mortality ◽

Inflammatory Drugs

AbstractColorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. There are well-established screening protocols involving fecal testing, radiographic, and endoscopic evaluations that have led to decreased incidence and mortality of CRC in the United States. In addition to screening for CRC, there is interest in preventing colorectal neoplasia by targeting the signaling pathways that have been identified in the pathway of dysplasia progressing to carcinoma. This review will detail the efficacy of multiple potential preventative strategies including lifestyle changes (physical activity, alcohol use, smoking cessation, and obesity); dietary factors (dietary patterns, calcium, vitamin D, fiber, folate, and antioxidants and micronutrients); and chemopreventive agents (nonsteroidal anti-inflammatory drugs, statins, metformin, bisphosphonates, and postmenopausal hormonal therapy).

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Advances in understanding the relationship between dietary factors and risk of colorectal cancer

World Chinese Journal of Digestology ◽

10.11569/wcjd.v18.i19.2033 ◽

2010 ◽

Vol 18 (19) ◽

pp. 2033

Author(s):

Li-Hong Sun

Keyword(s):

Colorectal Cancer ◽

Dietary Factors ◽

The Relationship

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Nutritional prevention of colorectal cancer

Proceedings of The Nutrition Society ◽

10.1017/s0029665120000051 ◽

2020 ◽

pp. 1-6

Author(s):

Mark A. Hull

Keyword(s):

Colorectal Cancer ◽

Risk Reduction ◽

Nutritional Therapy ◽

Health Impact ◽

Dietary Factors ◽

Processed Meat ◽

Intentional Weight Loss ◽

Nutritional Interventions ◽

Mechanistic Understanding ◽

Risk Reduction Measures

The preventability estimate for colorectal cancer (CRC) is approximately 50%, highlighting the huge potential for altering modifiable lifestyle factors (including diet and body fatness) in order to reduce risk of this common malignancy. There is strong evidence that dietary factors (including intake of wholegrains, fibre, red and processed meat and alcohol) affect CRC risk. The lack of positive intervention trials and limited mechanistic understanding likely explain limited public health impact of epidemiological observations, to date. An alternative strategy for nutritional prevention of CRC is use of supplements that provide higher individual nutrient exposure than obtained through the diet (chemoprevention). There are positive data for calcium and/or vitamin D and the n-3 fatty acid EPA from polyp prevention trials using colorectal adenoma as a CRC risk biomarker. Although CRC is an obesity-related malignancy, there remains a paucity of observational data supporting intentional weight loss for CRC risk reduction. Some types of obesity surgeries (Roux-en-Y gastric bypass) might actually increase subsequent CRC risk due to alteration of local intestinal factors. There is intense interest in nutritional therapy of patients after diagnosis of CRC, in order to impact on recurrence and overall survival (now often termed cancer interception). In conclusion, nutritional prevention of CRC continues to hold much promise. Increased mechanistic understanding of the role of individual nutrients (linked to intestinal microbiota), as well as a precision medicine approach to CRC chemoprevention and interception based on both tumour and host factors, should enable translation of nutritional interventions into effective CRC risk reduction measures.

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A Reasonable Diet Promotes Balance of Intestinal Microbiota: Prevention of Precolorectal Cancer

BioMed Research International ◽

10.1155/2019/3405278 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Pan Huang ◽

Yi Liu

Keyword(s):

Colorectal Cancer ◽

Intestinal Microflora ◽

Molecular Mechanisms ◽

Red Meat ◽

Dietary Factors ◽

High Protein ◽

Processed Meat ◽

High Fat ◽

Intestinal Microbes ◽

High Fibre

Colorectal cancer (CRC) is a multifactorial disease and the second leading cause of cancer death worldwide. The pathogenesis of colorectal cancer includes genetics, age, chronic inflammation, and lifestyle. Increasing attention has recently been paid to dietary factors. Evidence from epidemiological studies and clinical research suggests that high-fibre diets can significantly reduce the incidence of CRC, whilst the consumption of high-fat diets, high-protein diets, red meat, and processed meat is high-risk factors for tumorigenesis. Fibre is a regulator of intestinal microflora and metabolism and is thus a key dietary component for maintaining intestinal health. Intestinal microbes are closely linked to CRC, with the growth of certain microbiota (such as Fusobacterium nucleatum, Escherichia coli, or Bacteroides fragilis) favouring carcinogenesis, whilst the dominant microbiota population of the intestine, such as Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria, have multiple mechanisms of antitumour activity. Various dietary components have direct effects on the types of intestinal microflora: in the Western diet mode (high-fat, high-protein, and red meat), the proportion of conditional pathogens in the intestinal flora increases, the proportion of commensal bacteria decreases, and the occurrence of colorectal cancer is promoted. Conversely, a high-fibre diet can increase the abundance of Firmicutes and reduce the abundance of Bacteroides and consequently increase the concentration of short-chain fatty acids (SCFAs) in the intestine, inhibiting the development of CRC. This article reviews the study of the relationship between diet, intestinal microbes, and the promotion or inhibition of CRC and analyses the relevant molecular mechanisms to provide ideas for the prevention and treatment of CRC.

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