A pilot study on clinicopathological features and intestinal microflora changes in colorectal cancer patients born over a nine-year period encompassing three years before and after the Great Chinese famine

Li, Jiante; Wei, Zhiliang; Cao, Shougen; Tan, Xiaojie; Liu, Shanglong; Yao, Zengwu; Sun, Tiantian; Li, Yi; Zhang, Dongfeng; Zhou, Yanbing

doi:10.1016/j.canep.2019.02.001

Cited by 10 publications

(12 citation statements)

References 39 publications

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“…Nevertheless, it has been proposed that early-life alterations of signaling molecules might persist until adulthood due to an accumulation effect over the years, by epigenetic changes, or by alterations in the gut microbiota. [16][17][18][19][20] A common downstream effect of insulin, IGF-1, and leptin is the activation of the PI3K/Akt-signaling pathway, whereas adiponectin counteracts activation of this pathway. 21 Besides its well-known oncogenic effects, activation of the PI3K/Akt-signaling pathway has been shown to induce aerobic glycolysis by upregulation of several transporter proteins and (glycolytic) enzymes.…”

Section: Introductionmentioning

confidence: 99%

Energy balance‐related factors in childhood and adolescence and risk of colorectal cancer expressing different levels of proteins involved in the Warburg‐effect

Jenniskens

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Simons

et al. 2022

Intl Journal of Cancer

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Early-life (childhood to adolescence) energy balance-related factors (height, energy restriction, BMI) have been associated with adult colorectal cancer (CRC) risk.Warburg-effect activation via PI3K/Akt-signaling might explain this link. We investigated whether early-life energy balance-related factors were associated with risk of Warburg-subtypes in CRC. We used immunohistochemistry for six proteins involved in the Warburg-effect (LDHA, GLUT1, MCT4, PKM2, P53, and PTEN) on tissue microarrays of 2399 incident CRC cases from the prospective Netherlands Cohort Study (NLCS). Expression levels of all proteins were combined into a pathway-based sum score and categorized into three Warburg-subtypes (Warburg-low/-moderate/high). Multivariable Cox-regression analyses were used to estimate associations of height, energy restriction proxies (exposure to Dutch Hunger Winter; Second World War [WWII]; Economic Depression) and adolescent BMI with Warburg-subtypes in CRC. Height was positively associated with colon cancer in men, regardless of Warburg-subtypes, and with Warburg-low colon and Warburg-moderate rectal cancer in women. Energy restriction during the Dutch Hunger Winter was inversely associated with colon cancer in men, regardless of Warburg-subtypes. In women, energy restriction during the Hunger Winter and WWII was inversely associated with Warburg-low colon cancer, whereas energy restriction during the Economic Depression was positively associated with Warburg-high colon cancer. Adolescent BMI was positively associated with Warburg-high colon cancer in men, and Warburgmoderate rectal cancer in women. In conclusion, the Warburg-effect seems to be involved in associations of adolescent BMI with colon cancer in men, and of energy restriction during the Economic Depression with colon cancer in women. Further research is needed to validate these results.

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Section: Introductionmentioning

confidence: 99%

Energy balance‐related factors in childhood and adolescence and risk of colorectal cancer expressing different levels of proteins involved in the Warburg‐effect

Jenniskens

Offermans

Simons

et al. 2022

Intl Journal of Cancer

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“…The absence of caloric restriction during childhood may negatively impact microbial composition and may contribute to epigenetic dysregulation and development of CRC later in adulthood ( 51 ). Subjects who were energy restricted during their childhood had decreased abundance of pathogenic species such as F. nucleatum, Bacteroides fragilis , and Escherichia coli in later life, compared to non-restricted subjects ( 51 ). F. nucleatum is specifically associated with genetic and epigenetic defects such as microsatellite instability (MSI) and CpG island methylator phenotype (CIMP), respectively ( 51 ).…”

Section: The Diet-gut Microbiome-epigenetics Axismentioning

confidence: 99%

“…Subjects who were energy restricted during their childhood had decreased abundance of pathogenic species such as F. nucleatum, Bacteroides fragilis , and Escherichia coli in later life, compared to non-restricted subjects ( 51 ). F. nucleatum is specifically associated with genetic and epigenetic defects such as microsatellite instability (MSI) and CpG island methylator phenotype (CIMP), respectively ( 51 ). Similarly, consumption of high caloric foods could lead to histone modifications such as methylation and acetylation of the active enhancers, thus augmenting the gene expression pertaining to CRC.…”

Section: The Diet-gut Microbiome-epigenetics Axismentioning

confidence: 99%

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

et al. 2021

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Dietary factors have important role in modulating the gut microbiome, which in-turn regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome are decisive factors in colorectal cancer (CRC) tumorigenesis. Altered gut microbiome is associated with impaired immune response, and the release of carcinogenic or genotoxic substances which are the major microbiome-induced mechanisms implicated in CRC pathogenesis. Diets low in dietary fibers and phytomolecules as well as high in red meat are important dietary changes which predispose to CRC. Dietary fibers which reach the colon in an undigested form are further metabolized by the gut microbiome into enterocyte friendly metabolites such as short chain fatty acid (SCFA) which provide anti-inflammatory and anti-proliferative effects. Healthy microbiome supported by dietary fibers and phytomolecules could decrease cell proliferation by regulating the epigenetic events which activate proto-oncogenes and oncogenic pathways. Emerging evidence show that predominance of microbes such as Fusobacterium nucleatum can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. Synbiotics can protect the intestinal mucosa by improving immune response and decreasing the production of toxic metabolites, oxidative stress and cell proliferation. In this narrative review, we aim to update the emerging evidence on how diet could modulate the gut microbial composition and revive colonic epithelium. This review highlights the importance of healthy plant-based diet and related supplements in CRC prevention by improving the gut microbiome.

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“…Genetic alterations and epigenetic changes, such as global and regional hypermethylation of CpG islands are the hallmarks of human cancer, which may result in the activation of oncogenes and the inactivation of tumor-suppressor genes [10][11][12].A subgroup of CRC with frequent aberrant DNA methylations of the CpG island has been reported, referred to as the CIMP.…”

Section: Introductionmentioning

confidence: 99%

CpG Island Methylator Phenotype(CIMP) is An Independent Prognostic Marker with Tumor-Promoting Functions in Colorectal Cancer

et al. 2020

Preprint

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BackgroundThe CpG island methylator phenotype(CIMP)with extensive promoter methylation isa distinct epigenotype incolorectal cancer (CRC). Changes in microbiota and epigenetic dysregulation mightbe the key underlying mechanism.MethodsTissueswith stages I–III cancerwere collected afterproctocolectomy. The 16S rRNA gene sequencing was carried to determine the differences in microbiota.Subsequently,BRAF mutation,the statusof microsatellite instability (MSI, also known as mismatch repair deficiency) and CIMP were also tested. The Chi-square test was carriedoutto analyze the relationship between molecular changes (MSI and CIMP) and the development of CRC.ResultsPatients in the three groups differed in thetumorlocation(P=0.034) and the carcinoembryonic antigen (CEA) level (P=0.036).The positive CIMP and MSI-LOW/MSS were more common in the worse prognosis groups.The Kaplan–Meier and Cox proportional regression analyses indicated that CIMP and MSI were the independent indicators of poor survival since the positive rates of which were significantly higher in the non-survival group. Besides, there were differences in microbiota among tumor tissues of different prognoses, with the Fusobacterium nucleatum and Bacteroides fragilis more abundant in the worse prognosis groups.ConclusionThe persistent epigenetic changes influence the prognosis of patients with CRC and the composition of the gut microbiota might be the cause.

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A pilot study on clinicopathological features and intestinal microflora changes in colorectal cancer patients born over a nine-year period encompassing three years before and after the Great Chinese famine

Cited by 10 publications

References 39 publications

Energy balance‐related factors in childhood and adolescence and risk of colorectal cancer expressing different levels of proteins involved in the Warburg‐effect

Energy balance‐related factors in childhood and adolescence and risk of colorectal cancer expressing different levels of proteins involved in the Warburg‐effect

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

CpG Island Methylator Phenotype(CIMP) is An Independent Prognostic Marker with Tumor-Promoting Functions in Colorectal Cancer

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