Early onset sporadic colorectal cancer: Worrisome trends and oncogenic features

Cavestro, Giulia Martina; Mannucci, Alessandro; Zuppardo, Raffaella Alessia; Leo, Milena Di; Stoffel, Elena M.; Tonon, Giovanni

doi:10.1016/j.dld.2018.02.009

Cited by 83 publications

(84 citation statements)

References 226 publications

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“…and multistage processat each stage of that exogenous and endogenous risks factors associated with CRC can be involved. However, none of these factors should be considered specific for EOCRC [4]. Smoking and alcohol consumption, a diet with a high content of red meat and fast food, a hypodynamic lifestyle are generally acknowledged as risk factors for CRC.…”

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

“…Diabetes mellitus increases the risk of the development of gut neoplasms by 38%. Each 5 th excess in body mass index is associated with a 13-18% increase in the risk of CRC [4]. Chronic inflammation and gastrointestinal dysbiosis are also considered to be triggers of oncogenesis in the colon epithelium.…”

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

“…However, the majority of patients with EOCRC is characterized by the absence of family cases of CRC in the first and second generations [4], which is, on the whole, a specific feature of EOCRC. After the exclusion of family history factor along with exluding of inflammatory bowel diseases, the majority of patients with EOCRC could be included in the cohort of patients with the general population risk of CRC [4].…”

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

“…In turn, negative family history does not mean that the disease is not inherited or a patient with EOCRC is not a carrier of germline mutations [4]. Thus, less than a half of the patients with Lynch syndrome meets the "Amsterdam" criteria; the pathological MSH6-and PMS2-genotype is characterized by incomplete penetrance; familial adenomatous polyposis (less common, Lynch syndrome) is associated with pathogenic germinal mutations de-novo in the APC gene in approximately 15% of all the cases.…”

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

“…A high level of microsatellite instability can be detected in 21% of all the EOCRC cases and nearly in all of these positive cases, Lynch syndrome is subsequently proved by MMR-genotyping . Hypermethylation of the promoter region of the MLH1 gene along with the presence or absence of somatic BRAF-mutations in young patients with MSI-High-CRC is quite a rare event (p=0.006 [4]). This combination was revealed only in two studies.…”

Section: Msi-high Eocrcmentioning

confidence: 99%

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Molecular and Genetic Features of Colorectalcancer in Young Patients

Semyanikhina¹,

Pospekhova²

2019

MPSES

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The literature review represents the current state of research on molecular and genetic features of colorectal cancer in young patients. A steady increase in the incidence of colorectal cancer among young patients has been noted over recent years. Along with hereditary factors determining a high risk of colon tumours in patients who are carriers of germinal mutations in the genes responsible for the development of syndrome pathology (such as Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome, etc.), molecular and genetic changes in the cells of the colonic epithelium define the distinctive clinical and morphological features, prognosis, and response to specific therapy in young patients with colorectal cancer. To date, the main pathogenetic pathways involved in the promotion of carcinogenesis in the gut epithelium tissue have been identified: chromosomal instability, microsatellite instability, epigenetic abnormalities includinghyper-or hypomethylation of the tumour genome. Despite the well-studied molecular carcinogenesis of colorectal cancer, there are still many gaps in theunderstanding of the nature of such malignant neoplasms in patients with the disease diagnosed at an early age.

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Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

Section: Risk Factors For the Development Of Eocrc The Carcinogenesimentioning

confidence: 99%

Section: Msi-high Eocrcmentioning

confidence: 99%

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Molecular and Genetic Features of Colorectalcancer in Young Patients

Semyanikhina¹,

Pospekhova²

2019

MPSES

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Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women

et al. 2019

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Importance: Colorectal cancer incidence and mortality among individuals under age 50 (young-onset CRC) are rising. The reasons for such increase are largely unknown, although the surging prevalence of obesity may be partially responsible. Objective: To investigate prospectively the association between obesity and weight gain since early adulthood with risk of young-onset CRC. Design: Prospective cohort. Setting: U.S.-based Nurses’ Health Study II. Participants: 85,256 women aged 25 to 44 years free of cancer and inflammatory bowel disease at enrollment were followed from 1989 to 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Exposures: Current body mass index (BMI), BMI at age 18, and weight gain since age 18. Main Outcomes and Measures: Relative risk (RR) for incident young-onset CRC. Results: We documented 114 cases of young-onset CRC during 1,196,452 person-years of follow-up. Compared to women with BMI 18.5–22.9 kg/m2, the multivariable RR was 1.37 [95% confidence interval (CI): 0.81–2.30] for overweight women (BMI 25–29.9 kg/m2) and 1.93 (95% CI: 1.15–3.25) for obese women (BMI ≥ 30 kg/m2). The RR for each 5 kg/m2 increment in BMI was 1.20 (95% CI: 1.05–1.38, P-trend=0.01). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at age 18 and weight gain since age 18 contributed to this observation. Compared to women with BMI 18.5–20.9 kg/m2 at age 18, the RR of young-onset CRC was 1.63 (95% CI: 1.01–2.61) for women with BMI ≥ 23 kg/m2 at age 18 (P-trend=0.66). Similarly, compared to women who had gained < 5 kg or had lost weight, the RR of young-onset CRC was 2.15 (95% CI: 1.01–4.55) for women with ≥ 40 kg weight gain since age 18 (P-trend=0.007). Conclusion and Relevance: Obesity was associated with an increased risk of young-onset CRC among women. Further investigations among men and to elucidate underlying biological mechanisms are warranted.

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Anti‐colorectal cancer targets of resveratrol and biological molecular mechanism: Analyses of network pharmacology, human and experimental data

Song

et al. 2019

J of Cellular Biochemistry

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In this study, colorectal cancer (CRC)-diseased targets and resveratrol (Res)associated targets were combined and constructed by the use of grouped databases for identification of the predicted targets. After production of target-functional protein interaction network of Res anti-CRC, the topological analysis was used to create the core targets of Res anti-CRC. All core targets performed the analyses of biological function and pathway enrichment to optimize the biological processes and key signaling pathways of Res anti-CRC. The resultant five core therapeutic targets of Res anti-CRC were identified as protein kinase B1 (AKT1), interleukin 6 (IL6), Tumor protein p53 (TP53), vascular endothelial growth factor, and mitogenactivated protein kinase 1, respectively. Biological processes of Res anti-CRC were predominantly associated with regulating apoptosis, immune response, cellular communication, signal transduction, and metabolism of the nuclide. In addition, the top 10 key signaling pathways were identified, respectively. In human CRC sample assays, CRC histologic sections showed elevated expression of AKT1 and IL6 proteins, accompanied with abnormal changes in blood molecules. In pharmacological experiments of Res anti-CRC in vitro, Res-treated HCT116 cells showed inhibited cell growth, induced cell death. In addition, downregulation of intracellular AKT1 and IL6 expression were checked in Res-treated HCT116 cells.Taken together, these bioinformatic findings and preliminary validated data uncovered pharmacological molecular mechanisms associated with Res anti-CRC, and further identified top five core therapeutic targets. Beneficially, these five predicted targets might serve as potential biomolecules for anti-CRC treatment. K E Y W O R D Sbiotarget, mechanism, network pharmacology, resveratrol (Res)

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Early onset sporadic colorectal cancer: Worrisome trends and oncogenic features

Cited by 83 publications

References 226 publications

Molecular and Genetic Features of Colorectalcancer in Young Patients

Molecular and Genetic Features of Colorectalcancer in Young Patients

Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women

Anti‐colorectal cancer targets of resveratrol and biological molecular mechanism: Analyses of network pharmacology, human and experimental data

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