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1.
Dietary Factors Modulating Colorectal Carcinogenesis.
Vernia, F, Longo, S, Stefanelli, G, Viscido, A, Latella, G
Nutrients. 2021;(1)
Abstract
The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.
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Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies.
Veettil, SK, Wong, TY, Loo, YS, Playdon, MC, Lai, NM, Giovannucci, EL, Chaiyakunapruk, N
JAMA network open. 2021;(2):e2037341
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Abstract
IMPORTANCE Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate. OBJECTIVE To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC. DATA SOURCES MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019. EVIDENCE REVIEW Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. RESULTS From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses. CONCLUSIONS AND RELEVANCE This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
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The Effect of Perioperative Administration of Probiotics on Colorectal Cancer Surgery Outcomes.
Pitsillides, L, Pellino, G, Tekkis, P, Kontovounisios, C
Nutrients. 2021;(5)
Abstract
The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome's balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.
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4.
Preoperative malnutrition in patients with colorectal cancer.
Gupta, A, Gupta, E, Hilsden, R, Hawel, JD, Elnahas, AI, Schlachta, CM, Alkhamesi, NA
Canadian journal of surgery. Journal canadien de chirurgie. 2021;(6):E621-E629
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Abstract
Preoperative malnutrition in patients with colorectal cancer is associated with several postoperative consequences and poorer prognosis. Currently, there is a lack of a universal screening tool to assess nutritional status, and intervention to treat preoperative malnutrition is often neglected. This review summarizes and compares preoperative screening and interventional tools to help providers optimize malnourished patients with colorectal cancer for surgery. We found that nutritional screenings, such as the Subjectibe Global Assessment, Patient-Generated Subjective Global Assessment, Prognostic Nutritional Index, Nutrition Risk Index, Malnutrition Universal Screening Tool, Nutrition Risk Screening 2002, Nutrition Risk Score, serum albumin, and prealbumin, have all effectively predicted postoperative outcome. Physicians should consider which of these tools best fits their needs based on the their mode of assessment, efficiency, and specified parameters. Additionally, preoperative nutritional support, such as trimodal prehabilitation, modified peripheral parenteral nutrition, and N-3 fatty acid and arginine supplementation, which have also benefited patients postoperatively, ought to be implemented appropriately according to their ease of execution. Given the high prevalence of preoperative malnutrition in patients undergoing surgery for colorectal cancer, it is essential that health care providers assess and treat this malnutrition to reduce postoperative complications and length of hospital stay, and to improve prognosis to augment a patient's quality of care.La malnutrition préopératoire chez les patients atteints d'un cancer colorectal est associée à plusieurs complications postopératoires et à un pronostic plus sombre. Il n'existe actuellement aucun outil universel d'évaluation du statut nutritionnel, et les mesures visant à corriger la malnutrition préopératoire font souvent défaut. La présente revue résume et compare les outils de dépistage et d'intervention préopératoires pour aider les professionnels à améliorer l'état des patients dénutris qui doivent subir une chirurgie pour le cancer colorectal. Nous avons constaté que le dépistage nutritionnel à l'aide de questionnaires tels que l'Évaluation globale subjective, l'Index nutritionnel pronostique, l'Outil universel de dépistage de la malnutrition, NRS 2002 (Nutrition Risk Screening 2002), l'évaluation du risque nutritionnel, et le dosage de l'albumine et de la préalbumine sériques, a permis de prédire avec justesse l'issue de la chirurgie. Les médecins devraient vérifier lequel de ces outils est le mieux adapté à leurs besoins selon leur modalité d'évaluation, leur efficience et autres paramètres spécifiques. Également, un soutien nutritionnel préopératoire, comme la préadaptation trimodale, la nutrition parentérale périphérique modifiée et les suppléments d'acides gras N-3 et d'arginine, qui ont aussi donné des résultats postopératoires favorables, devrait être appliqué selon sa facilité d'administration. Étant donné la forte prévalence de la malnutrition préopératoire chez les patients soumis à une chirurgie pour cancer colorectal, les professionnels de la santé se doivent d'évaluer et de corriger la malnutrition afin de prévenir les complications postopératoires, d'abréger la durée du séjour hospitalier, et d'améliorer ainsi le pronostic et la qualité des soins.
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Gut microbiota alterations are distinct for primary colorectal cancer and hepatocellular carcinoma.
Jia, W, Rajani, C, Xu, H, Zheng, X
Protein & cell. 2021;(5):374-393
Abstract
Colorectal cancer (CRC) and hepatocellular carcinoma (HCC) are the second and third most common causes of death by cancer, respectively. The etiologies of the two cancers are either infectious insult or due to chronic use of alcohol, smoking, diet, obesity and diabetes. Pathological changes in the composition of the gut microbiota that lead to intestinal inflammation are a common factor for both HCC and CRC. However, the gut microbiota of the cancer patient evolves with disease pathogenesis in unique ways that are affected by etiologies and environmental factors. In this review, we examine the changes that occur in the composition of the gut microbiota across the stages of the HCC and CRC. Based on the idea that the gut microbiota are an additional "lifeline" and contribute to the tumor microenvironment, we can observe from previously published literature how the microbiota can cause a shift in the balance from normal → inflammation → diminished inflammation from early to later disease stages. This pattern leads to the hypothesis that tumor survival depends on a less pro-inflammatory tumor microenvironment. The differences observed in the gut microbiota composition between different disease etiologies as well as between HCC and CRC suggest that the tumor microenvironment is unique for each case.
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Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response.
Del Cornò, M, Varì, R, Scazzocchio, B, Varano, B, Masella, R, Conti, L
Cells. 2021;(7)
Abstract
Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.
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Early-onset colorectal cancer: initial clues and current views.
Hofseth, LJ, Hebert, JR, Chanda, A, Chen, H, Love, BL, Pena, MM, Murphy, EA, Sajish, M, Sheth, A, Buckhaults, PJ, et al
Nature reviews. Gastroenterology & hepatology. 2020;(6):352-364
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Abstract
Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research. In addition, we identify inconsistencies in the evidence implicating a strong effect of increased adiposity and suggest that certain behaviours (such as diet and stress) might place nonobese and otherwise healthy people at risk of this disease. Key risk factors are reviewed, including the global westernization of diets (usually involving a high intake of red and processed meats, high-fructose corn syrup and unhealthy cooking methods), stress, antibiotics, synthetic food dyes, monosodium glutamate, titanium dioxide, and physical inactivity and/or sedentary behaviour. The gut microbiota is probably at the crossroads of these risk factors and EOCRC. The time course of the disease and the fact that relevant exposures probably occur in childhood raise important methodological issues that are also discussed.
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Gene-environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta-analyses of observational studies.
Yang, T, Li, X, Montazeri, Z, Little, J, Farrington, SM, Ioannidis, JPA, Dunlop, MG, Campbell, H, Timofeeva, M, Theodoratou, E
International journal of cancer. 2019;(9):2315-2329
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Abstract
The cause of colorectal cancer (CRC) is multifactorial, involving both genetic variants and environmental risk factors. We systematically searched the MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases from inception to December 2016, to identify systematic reviews and meta-analyses of observational studies that investigated gene-environment (G×E) interactions in CRC risk. Then, we critically evaluated the cumulative evidence for the G×E interactions using an extension of the Human Genome Epidemiology Network's Venice criteria. Overall, 15 articles reporting systematic reviews of observational studies on 89 G×E interactions, 20 articles reporting meta-analyses of candidate gene- or single-nucleotide polymorphism-based studies on 521 G×E interactions, and 8 articles reporting 33 genome-wide G×E interaction analyses were identified. On the basis of prior and observed scores, only the interaction between rs6983267 (8q24) and aspirin use was found to have a moderate overall credibility score as well as main genetic and environmental effects. Though 5 other interactions were also found to have moderate evidence, these interaction effects were tenuous due to the lack of main genetic effects and/or environmental effects. We did not find highly convincing evidence for any interactions, but several associations were found to have moderate strength of evidence. Our conclusions are based on application of the Venice criteria which were designed to provide a conservative assessment of G×E interactions and thus do not include an evaluation of biological plausibility of an observed joint effect.
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Chemoprevention of colorectal cancer: Past, present, and future.
Umezawa, S, Higurashi, T, Komiya, Y, Arimoto, J, Horita, N, Kaneko, T, Iwasaki, M, Nakagama, H, Nakajima, A
Cancer science. 2019;(10):3018-3026
Abstract
Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer-related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well-established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of CRC. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non-steroidal anti-inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first-line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel "post-aspirin" agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger CRC prevention, but also to improvement of other obesity-related diseases.
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A Review of the In Vivo Evidence Investigating the Role of Nitrite Exposure from Processed Meat Consumption in the Development of Colorectal Cancer.
Crowe, W, Elliott, CT, Green, BD
Nutrients. 2019;(11)
Abstract
The World Cancer Research Fund (WCRF) 2007 stated that the consumption of processed meat is a convincing cause of colorectal cancer (CRC), and therefore, the public should avoid it entirely. Sodium nitrite has emerged as a putative candidate responsible for the CRC-inducing effects of processed meats. Sodium nitrite is purported to prevent the growth of Clostridium botulinum and other food-spoiling bacteria, but recent, contradictory peer-reviewed evidence has emerged, leading to media reports questioning the necessity of nitrite addition. To date, eleven preclinical studies have investigated the effect of consuming nitrite/nitrite-containing meat on the development of CRC, but the results do not provide an overall consensus. A sizable number of human clinical studies have investigated the relationship between processed meat consumption and CRC risk with widely varying results. The unique approach of the present literature review was to include analysis that limited the human studies to those involving only nitrite-containing meat. The majority of these studies reported that nitrite-containing processed meat was associated with increased CRC risk. Nitrite consumption can lead to the formation of N-nitroso compounds (NOC), some of which are carcinogenic. Therefore, this focused perspective based on the current body of evidence links the consumption of meat containing nitrites and CRC risk.