DNA hypermethylation of a selective gene panel as a risk marker for colon cancer in patients with ulcerative colitis

Kim, Tae-Oh; Park, Jongha; Kang, Myoung Joo; Lee, Sang‐Heon; Jee, Sam Ryong; Ryu, Dong Yup; Yang, Kwangmo; Yi, Joo Mi

doi:10.3892/ijmm.2013.1317

Cited by 34 publications

(25 citation statements)

References 29 publications

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“…Mutant mutp53 prolongs TNF-alpha-induced NF-kappaB activation which in mice harboring a germline p53 mutation causes severe tissue damage and a higher risk to CAC [85]. Mutated p53 caused a rapid development of high grade dysplasia, rapidly progressing to invasive carcinoma [85] DNA hypermethylation also is a typical feature of CAC [90]. Methylation of CpG islands in several genes can be found in chronically inflamed mucosa without visible dysplasia or lesion [61; 91].…”

Section: Crc In Chronic Colitis: What Is the Role Of Inflammation?mentioning

confidence: 99%

Chronic ulcerative colitis and colorectal cancer

2014

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One of the most important consequences of chronically active ulcerative colitis (UC) or Crohn's disease (CD) -the two major forms of inflammatory bowel disease (IBD) -is the development of colorectal cancer (CRC). An increased risk for the occurrence of CRC in up to 30% of affected patients after 35years of UC has been reported. Recent evidence from population based studies indicates a lower risk. Nevertheless the incidence is still significantly increased as compared to individuals without chronic colitis. Colitis-associated CRC (CAC) does not display the adenoma-carcinoma sequence which is typical for sporadic CRC and the pathophysiology appears to be different. Chronic inflammation and the increased turnover of epithelial cells contribute to the development of low-and high-grade dysplasia which may further transform into CAC. Reactive oxygen species (ROS) generated by the inflammatory infiltrate are thought to contribute to the generation of dysplastic lesions. In sporadic CRC the sequence of mutations that finally lead to malignancy involves early activation of Wnt/-catenin pathway (in 90% of cases) including mutations in adenomatous polyposis coli (APC) tumor suppressor gene, its regulating kinase GSK3 and -catenin itself. -catenin mutations are rarer in CAC and mutations in APC occur rather late during the disease progression, whereas there are earlier mutations in p53 and K-ras. Recent data indicate that the intestinal microbiome and its interaction with a functionally impaired mucosal barrier may also play a role in CAC development. CACs frequently show aggressive growth and early metastases. The treatment of CAC in patients with colitis always includes proctocolectomy with ileoanal anastomosis as meta-or synchronic lesions are frequent. AbstractOne of the most important consequences of chronically active ulcerative colitis

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Section: Crc In Chronic Colitis: What Is the Role Of Inflammation?mentioning

confidence: 99%

Chronic ulcerative colitis and colorectal cancer

2014

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“…DNA hypermethylation and microsatellite instability are also typical features and are frequently found at an early stage in IBD-associated CRC. In contrast, mutations in K-ras are relative infrequent [23,24]. Any particular genetic alteration that demonstrates a preferential or increased expression in dysplastic and neoplastic tissues might be thought of as a potential marker of cancer progression.…”

Section: Molecular Mechanisms Of Ibd-associated Colon Carcinogenesismentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

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Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ early biomarker in CRC that is related to transcriptional silencing of tumor suppressor genes and a marker for field cancerization [9][10][11] .…”

mentioning

confidence: 99%

Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

Hsu

Hsiao

Sun

et al. 2020

Sci Rep

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This study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/ advanced) were 8.04 (95% CI, 2.80-23.1; P for trend <0.01) and 8.01 (95% CI, 1.92-33.4; P for trend <0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.Colorectal cancer (CRC) is the second most frequently diagnosed cancer in women (614,000 cases, 9.2% of the total female population) and the third most frequently diagnosed cancer in men (746,000 cases, 10% of the total male population) worldwide 1-3 . The prognosis of and options of therapy for CRC rely on pathological stages, the staging system used (Dukes system or the TNM system), 5-year survival rate, and disease-free rate. It is fabulous for early-stage disease, ranging between 91% and 80% for histological stages I and II, in patients who can benefit from curative treatment, but it is poor in patients with isolated liver or lung metastases (5-year survival ≤20%) 4-7 . Over the past two decades, various treatment strategies have resulted in significant improvement in survival among patients with CRC 8 . Extensive studies have been executed to recognize novel prognostic and predictive biomarkers for CRC, including both genetic and epigenetic abnormalities. Previous studies have demonstrated that aberrant DNA methylation, the most frequent aberrant epigenetic modification in cancer, is an important

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DNA hypermethylation of a selective gene panel as a risk marker for colon cancer in patients with ulcerative colitis

Cited by 34 publications

References 29 publications

Chronic ulcerative colitis and colorectal cancer

Chronic ulcerative colitis and colorectal cancer

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan

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