Recent Progress in Nutrition (ISSN 2771-9871) is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. This periodical is devoted to publishing high-quality papers that describe the most significant and cutting-edge research in all areas of nutritional sciences. Its aim is to provide timely, authoritative introductions to current thinking, developments and research in carefully selected topics. Also, it aims to enhance the international exchange of scientific activities in nutritional science and human health.

Recent Progress in Nutrition publishes high quality intervention and observational studies in nutrition. High quality systematic reviews and meta-analyses are also welcome as are pilot studies with preliminary data and hypotheses generating studies. Emphasis is placed on understanding the relationship between nutrition and health and of the role of dietary patterns in health and disease.

Topics contain but are not limited to:

  • Macronutrients
  • Micronutrients
  • Essential nutrients
  • Bioactive nutrients
  • Nutrient requirements
  • Nutrient sources
  • Human nutrition aspects
  • Functional foods
  • Nutraceuticals
  • Health claims
  • Public health
  • Diet-related disorders
  • Metabolic syndrome
  • Malnutrition
  • Nutritional supplements
  • Sport nutrition

It publishes a variety of article types: Original Research, Review, Communication, Opinion, Comment, Conference Report, Technical Note, Book Review, etc.

There is no restriction on paper length, provided that the text is concise and comprehensive. Authors should present their results in as much detail as possible, as reviewers are encouraged to emphasize scientific rigor and reproducibility.

Publication Speed (median values for papers published in 2023): Submission to First Decision: 6.7 weeks; Submission to Acceptance: 16.1 weeks; Acceptance to Publication: 6 days (1-2 days of FREE language polishing included)

Current Issue: 2024  Archive: 2023 2022 2021
Open Access Review

Role of Diet in the Pathogenesis of Colorectal Polyps and Cancer

Ankit Patel 1, Kevin Houston 2, Michael Saadeh 3, Ana Vilela 3, Byung Soo Yoo 4, Steve M. D’Souza 3, David A. Johnson 5,*

  1. Department of Internal Medicine, George Washington University, Washington DC, United States

  2. Department of Internal Medicine, Virginia Commonwealth University, Richmond VA, United States

  3. Department of Internal Medicine, Eastern Virginia Medical School, Norfolk VA, United States

  4. Division of Gastroenterology, Department of Internal Medicine, Carolinas Medical Center, Charlotte NC, United States

  5. Division of Gastroenterology, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk VA, United States

Correspondence: David A. Johnson

Academic Editor: Célia C.G. Silva

Special Issue: Role of Diets, Vitamins, and Minerals in Cancers and Various Diseases

Received: April 24, 2022 | Accepted: July 28, 2022 | Published: August 01, 2022

Recent Progress in Nutrition 2022, Volume 2, Issue 3, doi:10.21926/rpn.2203018

Recommended citation: Patel A, Houston K, Saadeh M, Vilela A, Yoo BS, D’Souza SM, Johnson DA. Role of Diet in the Pathogenesis of Colorectal Polyps and Cancer. Recent Progress in Nutrition 2022; 2(3): 018; doi:10.21926/rpn.2203018.

© 2022 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.


Colorectal cancer (CRC) is currently the third most common cancer within the United States among both males and females, with increasing rates occurring in younger individuals compared to the past. Multiple environmental and social aspects including diet may be contributing to this increase in CRC rates. The aim of this review is to examine foods containing high fructose corn syrup, processed meats, and red meats which have shown to be linked to an increase in incidence of CRC. These foods can be a cause for disruption in a healthy microbiome leading to dysbiosis, which can have downstream effects on CRC formation. With the current data showing evidence of potential triggers and associations leading to CRC, more studies are needed to help directly link these dietary components and their pathways to cancer formations.


Diet; nutrition; colorectal cancer; neoplasia; polyps; high fructose corn syrup; processed meats; red meats; dysbiosis; surveillance screening; microbiome

1. Introduction

There is growing evidence that specific dietary components may play a major role in the development of various metabolic diseases and cancer. The incidence of colon cancer has been increasing in younger individuals with smoking, alcohol, and sedentary lifestyle all being cited as risk factors [1]. Recent evidence has shown dietary components and behaviors may also play a large role in the development of colorectal cancer (CRC) [2]. This chapter will focus on recent studies showing an increase in dietary intake of high fructose corn syrup (HFCS), red and processed meats, and the role of the gut microbiome on colorectal polyps and CRC.

Colorectal cancer is the 3rd most common cancer in both men and women within the United States [3]. With increased screening rates with colonoscopy there seem to be decreasing rates of CRC in people greater than 65 years old; however, rates in people less than 65 seem to be increasing [3,4]. For example, a study done between 1974 and 2013 demonstrated, in an age-period cohort analysis, a trend for increasing risk of CRC in birth cohorts of adults younger than 50 years [5]. This trend has prompted the US Preventive Services Task force to recommend offering CRC screening for all asymptomatic adults without risk factors starting at age 45, reduced from the prior recommendation of age 45 for African Americans and age 50 for all others, which represents a significant change in the scope of CRC screening [6].

A recent study found that the incidence of CRC in young adults in nine high income countries, including the US has increased in the last 20 years. The pattern found was sharp in contrast to the rapid declines found in older adults [7]. One of the factors that may be playing a role is obesity, which in the setting of its rising prevalence in young adults was found to be associated with an increased risk of early onset CRC among women [8]. Researchers have set out to explain the drastic increase, and evidence of this increased incidence has been suggested to revolve around human environmental changes such as smoking, alcohol use, decreased physical activity, changes in diet such as increased consumption of red meat and processed foods and decreased intake of dietary fibers [9].

Another important factor to take into account is the colon microbiome, which may also be playing a role in the pathogenesis of CRC in younger patients, as bacterial composition demonstrates both a proximal-distal gradient as well as a luminal-mucosal gradient. Factors affecting this composition continue to be an active area of investigation, and may include diet, aging, sleep, and other environmental exposures [9,10]. For instance, a recent study in mice demonstrated that Fusobacterium nucleatum presence is involved in metastasis from primary colorectal tumor. Furthermore, tumors associated with F. nucleatum presence were responsive to antibiotic treatment and demonstrated decreased bacterial load, cancer cell proliferation, and tumor cell growth [11]. Observations like this one, have prompted researchers to investigate the microbiome’s role in carcinogenesis and carries implications for future therapeutic options for CRC, including antibiotics, probiotics, and stool transplantation [12].

2. High Fructose Corn Syrup and CRC

Dietary sugars have been a focus of interest as high intake has been associated with the development of obesity, diabetes, and cardiovascular disease [13,14]. High fructose corn syrup is the processed form of corn starch that contains free fructose and glucose. It has replaced the use of naturally found sugars in the United States due to its relatively low cost and flavor profile. The diverse utility allows it to be used in a variety of consumer goods ranging from canned foods, cereals, sweetened beverages, and fast-food products [13]. While the relationship between HFCS and cardiovascular health has been an area of focus, only recent data has shown a relationship between HFCS to colon polyps and CRC.

Mechanistically, most glucose absorption occurs in the small intestine enterocytes through the sodium-glucose co-transporter and a glucose transporter type 2 (GLUT2) mechanism [15]. The fructose pathway, however, is mediated by a passive transporter through GLUT5, also present in epithelial enterocytes. It has been demonstrated that as little as 5 g of fructose can overwhelm this passive transporter [16]. Rather than being absorbed, this luminal fructose burden instead gets delivered downstream to the colon, where it can be consumed by local flora, primarily in the right colon [17]. Many studies have begun to show that cancerous tissues have a higher expression of GLUT5 transporters, including CRC tissue [18].

In 2019, Gonclaves et al. [19] investigated the effect of HFCS using a mouse model. They compared adenomatous polyposis coli (APC) positive mice and administered daily HFCS compared to control mice. They administered to the mice 20 g of weight-adjusted HFCS, a human-dose equivalent of 1 soda a day. They found that those with HFCS had a large increase in tumor size and grade even in the absence of obesity and metabolic syndrome [19]. This uptake of fructose caused an effect through accelerating glycolysis and de novo lipogenesis. Although the pathogenesis and exact mechanisms are still being elucidated, the studies have shown that adding fructose to CRC cells grown in hypoxic environments allows those cells to survive longer than cells without fructose. This may be in part because the fructose was absorbed through the GLUT5 fructose transporter and then retained by the tumor cells. This leads to a shift of products throughout the glycolytic pathway and increased fatty acid metabolism to support tumor growth.

Furthermore, a key protein involved throughout the mechanism is pyruvate kinase M2 (PKM2) as studies have shown that when fructose is inhibited from binding to PKM2, colorectal cells and villi have poorer growth and metabolic activity [20]. The study was able to identify ketohexokinase (KHK) as an important key accelerator in tumor growth and may be an important target for future studies looking at therapeutic targeting in KRAS-mutant CRC [19]. KHK is a fatty acid synthesis enzyme that when inhibited, showed tumor growth is limited or decreased compared to uninhibited models and they could not utilize the fructose available. The above findings have been in mouse models, but offer compelling biochemical evidence that dietary mechanisms play a large role in CRC tumorigenesis and further studies are needed to define the suspected application in human models.

Prospective data shows an incremental cancer risk in the population. Joh et al. [21] evaluated development of early-CRC based on dietary trends and age. They prospectively analyzed 33,106 participants who provided their dietary intake behaviors during adolescence to determine the effects of high consumption of simple sugar and HFCS containing sweetened beverages [21]. There was an increased risk of 1.17 (95% CI, 1.05-1.31) for all adenomas and 1.30 (95% CI, 1.06-1.60) for high-risk adenomas. By location, the highest risk was for rectal adenomas, with an associated risk rate of 1.43 (95% CI, 1.10-1.86) [21].

Another study of 95,464 participants conducted by Hur et al. [22] looked at an associated risk between sugar-sweetened beverages (SSBs) and CRC. Compared with individuals who consumed less than 1 serving per week of SSBs in adulthood, women who consumed more than 2 servings per day had a more than doubled risk of CRC with a 16% higher risk per serving per day increase. Each serving per day increment of SSB intake in adolescents (13-18 years) was associated with a 32% increased risk of early-onset CRC. Furthermore, replacing each serving per day of SSB with other beverages (e.g. coffee or milk) in adulthood was associated with a risk reduction for early-onset CRC of 17-36% [22]. Further research studies are needed to determine exact mechanisms, but the above data offers a compelling argument that dietary modification at a systemic level is needed to battle the growing CRC trends across western countries.

Similarly, to the data emerging on colorectal polyps and CRC, studies have looked specifically into the colitis-associated diseases and their relationship to HFCS. Long standing gastrointestinal inflammatory disorders such as inflammatory bowel disease (IBD) (i.e. Crohn’s disease or Ulcerative colitis) increase the risk of CRC through long-standing inflammatory states [23]. Nishiguichi et al. [24] found procolitic effects of a high fructose diet could be reversed by switching mice to a control diet and thereby prevented a high fructose diet-induced worsening of acute colitis likely from similar mechanisms as mentioned above. Thus, by reducing chronic inflammation of disease states such as IBD, reducing fructose in the diet could be protective against colitis-associated cancers. Further studies should help elucidate the exact mechanisms involved.

3. Processed Foods, Red Meats, and CRC

The first major push that red meats and processed meats could be related to increased rates of CRC was the “Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective”, by the World Cancer Research Fund/American Institute for Cancer Research [25]. The report showed approximately a 37% increased risk of colon cancer for every 100 g/day increase in red and processed meats [25]. This was shown again in 2011 by Chan et al. [26] who was able to find similar data points by comparing studies from 1966-2011 with red meat and processed meat intake. The data showed an increase in CRC risk of about 14% for every 100 g/day increase of total red and processed meat intake and 25% increased risk for colon cancer [26]. The International Agency for Research on Cancer (IARC) in 2015 labeled red meats as “potentially carcinogenic” and processed meats as “carcinogenic” due to its effect on increased CRC [27]. More recently, a systematic review and meta-analysis of 148 prospective studies showed that processed meat consumption was significantly associated with a 21% greater colon cancer risk and total red and processed meat consumption was significantly associated with greater risk of colon cancer (RR = 1.21; 95% CI = 1.09 - 1.34) [28]. The processes to prepare and create processed foods lead to the potential sources of causing inflammation and biologic changes which increase the risk for malignancy formation.

The possible biologic mechanisms of red meats leading to cancer are heterocyclic amines (HCA), heme compounds, and N-nitroso compounds (NOC). HCAs, which are considered potential carcinogens, are produced when amino acids within the meat are cooked at very high temperatures [29]. Heme products within the meat have been shown to induce epithelial damage within the colon of mice [30], which leads to hyperproliferation of epithelial cells within the intestinal crypts [31]. Van Der Meer-Van Kraaij et al. [32] demonstrated in mice that heme products within the colon led to down regulation of pentraxin, a protein involved in inhibiting cellular apoptosis. Both of these pathways in mice show processes that heme products can directly and indirectly lead to formation of CRC by inducing uncontrolled growth. NOCs can act as DNA alkylating agents [33], which can lead to mutations promoting cellular growth and division [34]. Proteins from the meat can cause formation of hydrogen sulfide, ammonia, secondary bile acids, and phenolic compounds, which can all increase the risk for CRC [35]. Hydrogen sulfide which is produced mainly from large meat diets coming from mainly sulfur containing amino acids and preservatives with inorganic sulfur [36]. Sulfur metabolism can lead to disruption of mucus bilayer [37], which in turn can lead to DNA damage and inflammation [38]. A recent study with large prospective cohorts with relatively high rates of follow-up over 25 years found that long-term adherence to sulfur-based diets was associated with increased rates of CRC [39]. Dermadi et al. [40] showed that mice fed western diets, had a decrease in a specific intracellular bile acid transporter, FABP6, and these mice were found to have increased rates of CRC due to overall decreased rates of bile acid transport. The proposed mechanism was an overall disruption of lipid metabolism and bile acid transport which led to a decrease in the Farnesoid X receptor (FXR) which is a key protein involved in bile acid homeostasis [41]. FXR deficiency has been seen to increase intestinal cell proliferation and inflammation in murine models and leading to carcinogenesis [42].

4. Protective Foods/Minerals Against CRC

Vitamin D – Vitamin D is known as a fat-soluble vitamin which is produced from ergocalciferol and cholecalciferol, which can be found in some fortified foods, ultimately leads to the production of calcitriol. Vitamin D has been hypothesized to reduce overall risk of cancer, given the regulation of calcitriol in multiple signaling pathways involving proliferation, apoptosis [43], and angiogenesis [44,45]. Calcitriol leads to reduction in proliferation from multiple mechanisms including down regulation of cyclin-dependent kinases (CDK), induction of CDK inhibitors [46], leading to growth arrest, and interfering with proliferative signaling pathways involving epidermal growth factor [47], and insulin like growth factor II [48,49]. Observational studies have shown people with CRC tend to have increased rates of vitamin D deficiency. A study of over 115,000 female patients, from age 25 to 42 from 1991-2015, showed that increased vitamin D within the diet, led to decreased rates of early on-set CRC [50]. Similarly, it has been seen in other studies that higher circulating levels of 25-hydroxy vitamin D in women compared to women with lower levels have a lower risk for CRC [51].

Fiber – Fiber is defined as plant material composed of cellulose, lignin and pectin. The primary proposed mechanisms for reduction of CRC are reducing fecal transit times and diluting the potential carcinogens thus reducing carcinogens binding to the gastrointestinal epithelium and maintaining the cell integrity [52]. Other proposed mechanisms are absorption of heterocyclic amines which affects overall bile acid metabolism [53] and increasing stimulation of anaerobic fermentation of the gut flora leading to increases in short-chain fatty acids (SCFAs), which are protective against CRC. Early observational studies showed an initial protective association between increased fiber intake and reduction in CRC [54,55]. In the past fiber intake was measured by overall intake of fruits and vegetables [56,57]. More recent data has been trying to isolate specific foods which are high in fiber and in the overall diet of most people. A recent meta-analysis found increasing consumption of whole grains, which consistent up to 7-15% fiber, from 15 g to 90 g/day led to up to 17% reduction in CRC [58]. There has been some data showing fiber and CRC might not have a specific association [59,60,61]. However, recall bias, selection bias, and sample size can lead to discrepancies between earlier case control and cohort studies [52]. Some attempts to reduce these discrepancies have been attempted such as with Dahm et al. [62] who had participants use food diaries to reduce the amount of recall bias, which showed intake of fiber was inversely associated with CRC. Overall, more data are needed, ideally from randomized control trials, to conclusively state if fiber is inversely associated with CRC.

Flavonoids – Polyphenols are a group of compounds found in several plant foods and drinks, including teas, vegetables, and fruits. Flavonoids, a class of polyphenols, have a demonstrated anti-inflammatory role explored in various conditions, including inflammatory bowel disease [63,64,65]. Their presence has been theorized as a potential reason for the protective effect of these foods and beverages in preventing various inflammation-mediate conditions, including malignancy. In-vitro and in-vivo models have also demonstrated an association between flavonoid intake and decreased carcinogenesis. One proposed mechanism for this effect is through effect on the commensal flora. Polyphenol intake has been associated with an increase in abundance of flora that produce SCFAs. Polyphenol intake also has direct effects on the intestinal mucosa and on barrier function. Several polyphenols, including those found in green tea, inhibit NFkB production and subsequently inhibit cyclooxygenase and inducible nitric oxide synthase production, thus decreasing the local inflammatory response [66]. An in-vitro analysis demonstrated decreased malignant conversion with the use of a bacterial flavonoid metabolite, 3,4-dihydroxyphenylacetic acid on cell lines treated with hemin, a carcinogenic metabolite of myoglobin [67]. Polyphenol metabolites, including epigallocatechin-3-gallate have demonstrated increase in the pro-apoptotic pathway, specifically through induction of p53 and caspases [68]. While polyphenol use has been explored for potential protective effects against CRC, their use has also demonstrated potential as an adjunct to chemotherapy and radiation therapy. Quercetin, a flavonoid found in many vegetables, has demonstrated increased effect of chemoradiation on CRC cells in-vitro [69]. Combination use of curcumin, a polyphenol found in turmeric, with traditional chemotherapy has demonstrated increased anti-tumor effect in prostate cancer cell lines [70]. While in-vitro and in-vivo studies have been promising, clinical trial data are needed to inform the preventative and therapeutic roles of polyphenols through.

β-Hydroxybutyrate (BHB) – BHB is a ketone body, which is used by the body for energy transfer in times of carbohydrate restriction, fasting, and during prolonged exercise [71]. BHB acts on a variety of different signaling pathways notably for hydroxycarboxylic acid receptor 2 (HCAR2), a surface G coupled receptor. HCAR2 activation within the gut epithelium leads to overall stabilization of the integrity of the gut membrane [72] and activation of the NLRP3 inflammasome [73] which has shown in mouse models to reduce colitis [71]. A recent study done by Dmitrieva-Posocco et al. [74] investigated the role of BHB and CRC via the activation of HOPX a negative regulator of tumorgenicity [75]. HPOX deficient mice did not respond to BHB, however the wild type models had decrease in tumor burden [74]. BHB was also shown to decrease growth of tumors in human cell lines that expressed both HCAR2 and HPOX [74]. While more studies are needed to confirm this in clinical trials, this shows promise for another avenue on preventing CRC and possibly using diet in conjunction with surgery and chemotherapy as an avenue for treatment of CRC.

5. Microbiome/Dysbiosis and CRC

The gut microbiome is a complex environment of various microorganisms and contains over 7000 different strains of bacteria [76]. It plays a large role in metabolism as well as communicates with the brain and immune system. Dysbiosis, caused by factors such as stress, diet, medications, and comorbidities, is implicated in a vast variety of chronic diseases, including inflammatory bowel disease and cancer. While the role of the microbiome in the development of colorectal carcinoma is not fully understood, there are several bacteria known to be significantly involved. F. nucleatum has been found in increased prevalence in adenomas and CRC, as well as metastasis of CRC [77]. F. nucleatum promotes CRC development through a multitude of pathways. In addition to invasion and release of proinflammatory cytokines from host cells, it inhibits apoptosis of infected cells via miRNA expression [77], inhibits CD4+ T cells to reduce antitumor immune response [78], and upregulates the Wnt pathway to promote growth of CRC cells [79]. Bifidobacterium and Faecalibacterium prausnitzii, on the other hand, have demonstrated anti-inflammatory properties and have specifically inhibited the development of preneoplastic lesions in chemically induced CRC [80]. Dysbiosis of these specific bacteria have been consistently reported in patients with CRC compared to health control groups [81]. Recent literature has studied the microbial ratio in hopes of identifying a biomarker for screening early CRC. The ratio of F. nucleatum/Bifidobacterium was found to have a sensitivity of 84.6% and a specificity of 92.3% in detecting CRC, and in combination with F. nucleatum/F. prausnitzii, detected 90.0% sensitivity and 60.0% specificity in detecting stage 1 of CRC [82]. With the knowledge that F. nucleatum displays strong antagonistic activity towards Bb and Fp, the negative correlation seen in CRC fecal samples is unsurprising.

Evidence of the above shifts in microbiome offers a potential opportunity for probiotic intervention. One study examined the effect of probiotics on the microbiota in patients with CRC and found a significant difference in microbiota diversity and alterations in the mucosa. When compared to placebo, the use of probiotics such as Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, was shown to have a 6-fold decrease in relative abundance of Fn [81]. An additional study examined the use of heat-killed Lb and its effects on Fn virulence factors in oral flora. They discovered a decrease in Fap2 virulence factor expression and subsequent host cell adhesion in the presence of heat-killed L. acidophilus [83]. Not only does this help prevent F. nucleatum/invasion and release of proinflammatory cytokines, but Fap2 has been recognized as a galactose-binding lectin. Notably, colorectal adenomas express high levels of Gal-GalNAc lectin, the Fap2 virulence factor which plays a large role in recruitment of F. nucleatum [83]. Although this study examined the effects on oral F. nucleatum, it should be considered that over 40% of patients with CRC exhibited identical strains of oral and CRC specimens, thus suggesting similar efficacy with colorectal F. nucleatum [84]. While studies show benefit in probiotic use against F. nucleatum CRC, further research is required to determine their use in prevention and treatment.

More broadly, pre- and pro- biotic foods have been explored to modify the risk of CRC. Fermented foods, especially yogurt, have been of particular interest due to their demonstrated effect on the composition of the colonic microbiome [85,86]. While the overall microbiome effects of specific fermented products vary, yogurt consumption has been associated with decreased risk of several cancers [86,87]. A large meta-analysis has demonstrated that high yogurt consumption is associated with low colon cancer risk [88].

6. Conclusion

With multiple factors playing a role into the formation of CRC, diet and gut health has emerged as an important component with a need to focus on changes earlier in life to decrease the overall risk of CRC. This is important as younger individuals are showing increased rates of CRC. Clearly, more protective interventive measures are indicated as possible mitigation strategies for protection. The ideal way would be eliciting dietary changes early in life, thereby potentially decreasing risk factors for CRC. Notably this would emphasize avoiding a fully “westernized diet” (characterized by proteins mainly from red and processed meats, saturated fats, corn-derived fructose syrup, and decreased amount of fruits and vegetables) [89]. Moving towards diets such as the Mediterranean diet, and plant-based meats could be healthier alternatives to reduce the chemicals which affect the gut microbiome in a favorable direction “Protective foods” in a diet such as fiber, fruits, vegetables, vitamin D, dairy products and fish products have shown to have risk reduction against CRC [90]. These foods have been shown to increase the biodiversity of the microbiota and reduce the incidence of more pathogenic bacteria. Clearly national guidelines have emphasized that earlier surveillance which has already been implemented with the change of routine colonoscopy for CRC screening shifting to the age of 45 from 50 [6]. Large strides in the reduction of the incidence of CRC has been made over the past decades and is important that expanding efforts to reduce the risk for the general population that may be exposed to the ramifications of a western diet.

Author Contributions

Dr Johnson DA contributed to the construction of the project; all authors wrote and edited the manuscript.

Competing Interests

The authors have declared that no competing interests exist.


  1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009; 22: 191-197. [CrossRef]
  2. Hofseth LJ, Hebert JR, Chanda A, Chen H, Love BL, Pena MM, et al. Early-onset colorectal cancer: Initial clues and current views. Nat Rev Gastroenterol Hepatol. 2020; 17: 352-364. [CrossRef]
  3. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021; 71: 7-33. [CrossRef]
  4. Song M, Chan AT, Sun J. Influence of the gut microbiome, diet, and environment on risk of colorectal cancer. Gastroenterology. 2020; 158: 322-340. [CrossRef]
  5. Siegel RL, Fedewa SA, Anderson WF, Miller KD, Ma J, Rosenberg PS, et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017; 109: djw322. [CrossRef]
  6. Davidson KW, Barry MJ, Mangione CM, Cabana M, Caughey AB, Davis EM, et al. Screening for colorectal cancer: Us preventive services task force recommendation statement. JAMA. 2021; 325: 1965-1977. [CrossRef]
  7. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017; 66: 683-691. [CrossRef]
  8. Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M, et al. Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncol. 2019; 5: 37-44. [CrossRef]
  9. Feng YL, Shu L, Zheng PF, Zhang XY, Si CJ, Yu XL, et al. Dietary patterns and colorectal cancer risk: A meta-analysis. Eur J Cancer Prev. 2017; 26: 201-211. [CrossRef]
  10. Flynn KJ, Ruffin MT, Turgeon DK, Schloss PD. Spatial variation of the native colon microbiota in healthy adults. Cancer Prev Res (Phila). 2018; 11: 393-402. [CrossRef]
  11. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, et al. Analysis of fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017; 358: 1443-1448. [CrossRef]
  12. Cass SH, Ajami NJ, White MG. The microbiome: The link to colorectal cancer and research opportunities. Curr Treat Options Oncol. 2022; 23: 631-644. [CrossRef]
  13. Malik VS, Hu FB. Fructose and cardiometabolic health: What the evidence from sugar-sweetened beverages tells us. J Am Coll Cardiol. 2015; 66: 1615-1624. [CrossRef]
  14. DeChristopher LR, Auerbach BJ, Tucker KL. High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans- the Jackson heart study. BMC Nutr. 2020; 6: 70. [CrossRef]
  15. Chen L, Tuo B, Dong H. Regulation of intestinal glucose absorption by ion channels and transporters. Nutrients. 2016; 8: 43. [CrossRef]
  16. Rumessen JJ, Gudmand-Høyer E. Absorption capacity of fructose in healthy adults. Comparison with sucrose and its constituent monosaccharides. Gut. 1986; 27: 1161-1168. [CrossRef]
  17. Zhang X, Grosfeld A, Williams E, Vasiliauskas D, Barretto S, Smith L, et al. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 2019; 33: 7126-7142. [CrossRef]
  18. Douard V, Ferraris RP. Regulation of the fructose transporter glut5 in health and disease. Am J Physiol Endocrinol Metab. 2008; 295: E227-237. [CrossRef]
  19. Goncalves MD, Lu C, Tutnauer J, Hartman TE, Hwang SK, Murphy CJ, et al. High-fructose corn syrup enhances intestinal tumor growth in mice. Science. 2019; 363: 1345-1349. [CrossRef]
  20. Zahra K, Dey T, Ashish, Mishra SP, Pandey U. Pyruvate kinase M2 and cancer: The role of PKM2 in promoting tumorigenesis. Front Oncol. 2020; 10: 159. [CrossRef]
  21. Joh HK, Lee DH, Hur J, Nimptsch K, Chang Y, Joung H, et al. Simple sugar and sugar-sweetened beverage intake during adolescence and risk of colorectal cancer precursors. Gastroenterology. 2021; 161: 128-142.e20. [CrossRef]
  22. Hur J, Otegbeye E, Joh HK, Nimptsch K, Ng K, Ogino S, et al. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021; 70: 2330-2336. [CrossRef]
  23. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn’s disease with colonic involvement. Lancet. 1990; 336: 357-359. [CrossRef]
  24. Nishiguchi R, Basu S, Staab HA, Ito N, Zhou XK, Wang H, et al. Dietary interventions to prevent high-fructose diet-associated worsening of colitis and colitis-associated tumorigenesis in mice. Carcinogenesis. 2021; 42: 842-852. [CrossRef]
  25. Wiseman M. The second world cancer research fund/American institute for cancer research expert report. Food, nutrition, physical activity, and the prevention of cancer: A global perspective. Proc Nutr Soc. 2008; 67: 253-256. [CrossRef]
  26. Chan DSM, Lau R, Aune D, Vieira R, Greenwood DC, Kampman E, et al. Red and processed meat and colorectal cancer incidence: Meta-analysis of prospective studies. PLoS One. 2011; 6: e20456. [CrossRef]
  27. Diallo A, Deschasaux M, Latino-Martel P, Hercberg S, Galan P, Fassier P, et al. Red and processed meat intake and cancer risk: Results from the prospective Nutrinet-Santé cohort study. Int J Cancer. 2018; 142: 230-237. [CrossRef]
  28. Farvid MS, Sidahmed E, Spence ND, Mante Angua K, Rosner BA, Barnett JB. Consumption of red meat and processed meat and cancer incidence: A systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2021; 36: 937-951. [CrossRef]
  29. Sinha R, Rothman N, Brown ED, Mark SD, Hoover RN, Caporaso NE, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res. 1994; 54: 6154-6159.
  30. Ijssennagger N, Rijnierse A, de Wit NJW, Boekschoten MV, Dekker J, Schonewille A, et al. Dietary heme induces acute oxidative stress, but delayed cytotoxicity and compensatory hyperproliferation in mouse colon. Carcinogenesis. 2013; 34: 1628-1635. [CrossRef]
  31. Ijssennagger N, Belzer C, Hooiveld GJ, Dekker J, van Mil SW, Müller M, et al. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. Proc Natl Acad Sci U S A. 2015; 112: 10038-10043. [CrossRef]
  32. Van Der Meer-Van Kraaij C, Van Lieshout EMM, Kramer E, Van Der Meer R, Keijer J. Mucosal pentraxin (Mptx), a novel rat gene 10-fold down-regulated in colon by dietary heme. FASEB J. 2003; 17: 1277-1285. [CrossRef]
  33. Zhao Z, Feng Q, Yin Z, Shuang J, Bai B, Yu P, et al. Red and processed meat consumption and colorectal cancer risk: A systematic review and meta-analysis. Oncotarget. 2017; 8: 83306-83314. [CrossRef]
  34. Bingham SA, Hughes R, Cross AJ. Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response. J Nutr. 2002; 132: 3522S-3525S. [CrossRef]
  35. Abu-Ghazaleh N, Chua WJ, Gopalan V. Intestinal microbiota and its association with colon cancer and red/processed meat consumption. J Gastroenterol Hepatol. 2021; 36: 75-88. [CrossRef]
  36. Dostal Webster A, Staley C, Hamilton MJ, Huang M, Fryxell K, Erickson R, et al. Influence of short-term changes in dietary sulfur on the relative abundances of intestinal sulfate-reducing bacteria. Gut Microbes. 2019; 10: 447-457. [CrossRef]
  37. Attene-Ramos MS, Wagner ED, Gaskins HR, Plewa MJ. Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res. 2007; 5: 455-459. [CrossRef]
  38. Ijssennagger N, van der Meer R, van Mil SWC. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med. 2016; 22: 190-199. [CrossRef]
  39. Wang Y, Nguyen LH, Mehta RS, Song M, Huttenhower C, Chan AT. Association between the sulfur microbial diet and risk of colorectal cancer. JAMA Netw Open. 2021; 4: e2134308. [CrossRef]
  40. Dermadi D, Valo S, Ollila S, Soliymani R, Sipari N, Pussila M, et al. Western diet deregulates bile acid homeostasis, cell proliferation, and tumorigenesis in colon. Cancer Res. 2017; 77: 3352-3363. [CrossRef]
  41. Hwang ST, Urizar NL, Moore DD, Henning SJ. Bile acids regulate the ontogenic expression of ileal bile acid binding protein in the rat via the farnesoid X receptor. Gastroenterology. 2002; 122: 1483-1492. [CrossRef]
  42. Maran RRM, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, et al. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther. 2009; 328: 469-477. [CrossRef]
  43. Kaler P, Augenlicht L, Klampfer L. Macrophage-derived IL-1beta stimulates Wnt signaling and growth of colon cancer cells: A crosstalk interrupted by vitamin D3. Oncogene. 2009; 28: 3892-3902. [CrossRef]
  44. Pendás-Franco N, García JM, Peña C, Valle N, Pálmer HG, Heinäniemi M, et al. DICKKOPF-4 is induced by TCF/β-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1α,25-dihydroxyvitamin D3. Oncogene. 2008; 27: 4467-4477. [CrossRef]
  45. Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014; 14: 342-357. [CrossRef]
  46. Toropainen S, Väisänen S, Heikkinen S, Carlberg C. The down-regulation of the human MYC gene by the nuclear hormone 1α,25-dihydroxyvitamin D3 is associated with cycling of corepressors and histone deacetylases. J Mol Biol. 2010; 400: 284-294. [CrossRef]
  47. Tong WM, Hofer H, Ellinger A, Peterlik M, Cross HS. Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: Relevance for suppression of epidermal growth factor-stimulated cell growth. Oncol Res. 1999; 11: 77-84.
  48. Oh YS, Kim EJ, Schaffer BS, Kang YH, Binderup L, MacDonald RG, et al. Synthetic low-calcaemic vitamin D3 analogues inhibit secretion of insulin-like growth factor II and stimulate production of insulin-like growth factor-binding protein-6 in conjunction with growth suppression of HT-29 colon cancer cells. Mol Cell Endocrinol. 2001; 183: 141-149. [CrossRef]
  49. Ferrer-Mayorga G, Larriba MJ, Crespo P, Muñoz A. Mechanisms of action of vitamin D in colon cancer. J Steroid Biochem Mol Biol. 2019; 185: 1-6. [CrossRef]
  50. Kim H, Lipsyc-Sharf M, Zong X, Wang X, Hur J, Song M, et al. Total vitamin D intake and risks of early-onset colorectal cancer and precursors. Gastroenterology. 2021; 161: 1208-1217.e9. [CrossRef]
  51. McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR, et al. Circulating vitamin d and colorectal cancer risk: An international pooling project of 17 cohorts. J Natl Cancer Inst. 2019; 111: 158-169. [CrossRef]
  52. Pericleous M, Mandair D, Caplin ME. Diet and supplements and their impact on colorectal cancer. J Gastrointest Oncol. 2013; 4: 409-423.
  53. Harris PJ, Triggs CM, Roberton AM, Watson ME, Ferguson LR. The adsorption of heterocyclic aromatic amines by model dietary fibres with contrasting compositions. Chem Biol Interact. 1996; 100: 13-25. [CrossRef]
  54. Howe GR, Benito E, Castelleto R, Cornée J, Estève J, Gallagher RP, et al. Dietary intake of fiber and decreased risk of cancers of the colon and rectum: Evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst. 1992; 84: 1887-1896. [CrossRef]
  55. Aune D, Chan DS, Lau R, Vieira R, Greenwood DC, Kampman E, et al. Dietary fibre, whole grains, and risk of colorectal cancer: Systematic review and dose-response meta-analysis of prospective studies. BMJ. 2011; 343: d6617. [CrossRef]
  56. Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology. 2011; 141: 106-118. [CrossRef]
  57. Song M, Garrett WS, Chan AT. Nutrients, foods, and colorectal cancer prevention. Gastroenterology. 2015; 148: 1244-1260.e16. [CrossRef]
  58. Gaesser GA. Whole grains, refined grains, and cancer risk: A systematic review of meta-analyses of observational studies. Nutrients. 2020; 12: 3756. [CrossRef]
  59. Asano T, McLeod RS. Dietary fibre for the prevention of colorectal adenomas and carcinomas. Cochrane Database Syst Rev. 2002: CD003430. doi: 10.1002/14651858.CD003430. [CrossRef]
  60. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med. 1999; 340: 169-176. [CrossRef]
  61. Michels KB, Edward G, Joshipura KJ, Rosner BA, Stampfer MJ, Fuchs CS, et al. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst. 2000; 92: 1740-1752. [CrossRef]
  62. Dahm CC, Keogh RH, Spencer EA, Greenwood DC, Key TJ, Fentiman IS, et al. Dietary fiber and colorectal cancer risk: A nested case-control study using food diaries. J Natl Cancer Inst. 2010; 102: 614-626. [CrossRef]
  63. Wu Z, Huang S, Li T, Li N, Han D, Zhang B, et al. Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis. Microbiome. 2021; 9: 184. [CrossRef]
  64. Oz HS, Chen T, de Villiers WJ. Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models. Front Immunol. 2013; 4: 132. [CrossRef]
  65. Brückner M, Westphal S, Domschke W, Kucharzik T, Lügering A. Green tea polyphenol epigallocatechin-3-gallate shows therapeutic antioxidative effects in a murine model of colitis. J Crohns Colitis. 2012; 6: 226-235. [CrossRef]
  66. Ding S, Xu S, Fang J, Jiang H. The protective effect of polyphenols for colorectal cancer. Front Immunol. 2020; 11: 1407. [CrossRef]
  67. Catalán M, Ferreira J, Carrasco-Pozo C. The microbiota-derived metabolite of quercetin, 3,4-dihydroxyphenylacetic acid prevents malignant transformation and mitochondrial dysfunction induced by hemin in colon cancer and normal colon epithelia cell lines. Molecules. 2020; 25:4138. [CrossRef]
  68. Hwang JT, Ha J, Park IJ, Lee SK, Baik HW, Kim YM, et al. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Lett. 2007; 247: 115-121. [CrossRef]
  69. Priego S, Feddi F, Ferrer P, Mena S, Benlloch M, Ortega A, et al. Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: A Bcl-2- and superoxide dismutase 2-dependent mechanism. Mol Cancer Ther. 2008; 7: 3330-3342. [CrossRef]
  70. Hour TC, Chen J, Huang CY, Guan JY, Lu SH, Pu YS. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBPβ expressions and suppressing NF-κB activation. Prostate. 2002; 51: 211-218. [CrossRef]
  71. Newman JC, Verdin E. β-hydroxybutyrate: A signaling metabolite. Annu Rev Nutr. 2017; 37: 51-76. [CrossRef]
  72. Graff EC, Fang H, Wanders D, Judd RL. Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2. Metabolism. 2016; 65: 102-113. [CrossRef]
  73. Macia L, Tan J, Vieira AT, Leach K, Stanley D, Luong S, et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat Commun. 2015; 6: 6734. [CrossRef]
  74. Dmitrieva-Posocco O, Wong AC, Lundgren P, Golos AM, Descamps HC, Dohnalová L, et al. β-hydroxybutyrate suppresses colorectal cancer. Nature. 2022; 605: 160-165. [CrossRef]
  75. Yamashita K, Katoh H, Watanabe M. The homeobox only protein homeobox (HOPX) and colorectal cancer. Int J Mol Sci. 2013; 14: 23231-23243. [CrossRef]
  76. Rebersek M. Gut microbiome and its role in colorectal cancer. BMC Cancer. 2021; 21: 1325. [CrossRef]
  77. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012; 22: 299-306. [CrossRef]
  78. Ranjbar M, Salehi R, Haghjooy Javanmard S, Rafiee L, Faraji H, Jafarpor S, et al. The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review. Cancer Cell Int. 2021; 21: 194. [CrossRef]
  79. Fan X, Jin Y, Chen G, Ma X, Zhang L. Gut microbiota dysbiosis drives the development of colorectal cancer. Digestion. 2021; 102: 508-515. [CrossRef]
  80. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008; 105: 16731-16736. [CrossRef]
  81. Gao Z, Guo B, Gao R, Zhu Q, Wu W, Qin H. Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer. Mol Med Rep. 2015; 12: 6119-6127. [CrossRef]
  82. Guo S, Li L, Xu B, Li M, Zeng Q, Xiao H, et al. A simple and novel fecal biomarker for colorectal cancer: Ratio of Fusobacterium nucleatum to probiotics populations, based on their antagonistic effect. Clin Chem. 2018; 64: 1327-1337. [CrossRef]
  83. Ding Q, Sun X, Cao S, Zhao C, Wang Y, Wang X. Heat-killed lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells. FEMS Microbiol Lett. 2021; 368: fnaa160. [CrossRef]
  84. Komiya Y, Shimomura Y, Higurashi T, Sugi Y, Arimoto J, Umezawa S, et al. Patients with colorectal cancer have identical strains of Fusobacterium nucleatum in their colorectal cancer and oral cavity. Gut. 2019; 68: 1335-1337. [CrossRef]
  85. Suzuki Y, Ikeda K, Sakuma K, Kawai S, Sawaki K, Asahara T, et al. Association between yogurt consumption and intestinal microbiota in healthy young adults differs by host gender. Front Microbiol. 2017; 8: 847. [CrossRef]
  86. Zhang K, Dai H, Liang W, Zhang L, Deng Z. Fermented dairy foods intake and risk of cancer. Int J Cancer. 2019; 144: 2099-2108. [CrossRef]
  87. Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms. 2020; 8: 1715. [CrossRef]
  88. Sun J, Song J, Yang J, Chen L, Wang Z, Duan M, et al. Higher yogurt consumption is associated with lower risk of colorectal cancer: A systematic review and meta-analysis of observational studies. Front Nutr. 2021; 8: 789006. [CrossRef]
  89. Statovci D, Aguilera M, MacSharry J, Melgar S. The impact of western diet and nutrients on the microbiota and immune response at mucosal interfaces. Front Immunol. 2017; 8: 838. [CrossRef]
  90. Thanikachalam K, Khan G. Colorectal cancer and nutrition. Nutrients. 2019; 11: 164. [CrossRef]
Download PDF Download Citation
0 0