Evaluation of The Usefulness of Testing for P53 Mutations in Colorectal Cancer Surveillance for Ulcerative Colitis

Lashner, Bret A.; Shapiro, Bradley D.; Husain, Adnan; Goldblum, John R.

doi:10.1111/j.1572-0241.1999.877_f.x

Cited by 97 publications

(44 citation statements)

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“…At a molecular level, p53 gene mutations or p53 protein overexpression, which is a late event in the development of sporadic colorectal carcinoma, have been commonly reported as early events in the dysplasia-carcinoma sequences in UC-associated carcinomas. [11][12][13][14] These results provide evidence that UC-associated cancer may develop along a pathway that is different from that of sporadic colorectal cancer.…”

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confidence: 75%

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Osawa

Nakajima

Fujisawa

et al. 2005

Intl Journal of Cancer

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Colon cancer is one of the most serious complications of inflammatory bowel diseases, especially ulcerative colitis (UC). Previous studies have shown that characteristic immunological event during inflammation in UC is the expression of T helper-type 2 (Th2) cell-derived cytokines. In this study, we investigated the influence of a predominant Th2-type cytokine response in colitis on carcinogen-induced colon tumors. Wild type (WT), interferon gamma (IFN-c) gene deficient (2/2) [Th2 dominant] or interleukin (IL)-4 2/2 [Th1-dominant] mice of BALB/c background were used in this study. To compare tumor formation, mice were given the carcinogen azoxymethane (AOM) and intrarectal administration of trinitrobenzene sulfonic acid (TNBS), to induce colitis. Thirtythree weeks after initial treatment, the total colon was examined. When IFN-c 2/2 mice were treated with AOM and TNBS, significantly higher number of tumors were seen (8.4 6 1.7) than in WT (3.3 6 2.9) or IL-4 2/2 (3.1 6 3.4) mice, which received identical treatments. A separate set of experiment, using less doses of AOM and TNBS also showed the higher frequency of tumor formation in IFN-c 2/2 mice than in IL-4 2/2 mice. Histologically, the tumors were well-or moderately-differentiated adenocarcinomas. No invasion into the submucosal or serosal layers of the intestine was seen. In immunohistological staining, some tumors in IFN-c 2/2 mice showed distinct nuclear expression of b-catenin, in contrast to the strong membrane staining seen in tumors of IL-4 2/2 mice. In conclusion, colonic inflammation associated with Th2-donimant cytokine responses enhanced the formation of malignant neoplasms. ' 2005 Wiley-Liss, Inc.

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mentioning

confidence: 75%

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Osawa

Nakajima

Fujisawa

et al. 2005

Intl Journal of Cancer

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“…Alterations in the TP53 gene, a late event in the pathogenesis of sporadic colorectal cancers, occur in dysplastic lesions with a background of ulcerative colitis (Yin et al, 1993;Holzmann et al, 1998) and are likely to proceed to dysplasia (Lashner et al, 1999). Thus, the increased TP53 mutation load in inflamed colonic epithelium of patients with IBD suggests that TP53 mutations in noncancerous colon tissue of IBD patients specifically confer susceptibility to the development of colorectal cancers in an inflammatory microenvironment (Hussain et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Targeting activation-induced cytidine deaminase prevents colon cancer development despite persistent colonic inflammation

et al. 2011

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“…Unlike in sporadic CRCs, IBD-associated cancer mutations and LOH in p53 are early events that can already be found in macroscopically normal looking mucosa [52][53][54] . In contrast, mutations in k-ras are relatively infrequent.…”

Section: Genetics Of Ulcerative Colitis Associated Colorectal Cancersmentioning

confidence: 98%

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Lakatos¹,

Lakatos²

2008

WJG

368

245

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Since the first report of an inflammatory bowel disease (IBD) case associated with colorectal cancer (CRC) by Crohn and Rosenberg [1] , significant efforts have been made to elucidate this presumed association. Nowadays, the association between IBD and the increased risk for CRC is widely accepted. Although CRC, complicating ulcerative colitis and Crohn's disease, accounts only for 1%-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 10%-15% of all deaths in IBD patients [2] . The age at diagnosis of CRC associated with IBD is 15-20 years earlier compared to sporadic cancers. In the meta-analysis by Eaden et al [3] , the average age at diagnosis was 43.2 years. Similarly, in a recent publication from Eastern Europe [4] , it was found to be 50.9 years, 10-15 years younger compared to sporadic CRC cases from the same area (62.2 years) [5] . According to US [6] and Canadian [7] publications, almost two-thirds of the affected patients were males, yet results are conflicting [4,8] . In addition, the frequency of multiple CRCs is higher than in patients with sporadic CRC [9] .The increased risk of CRC in UC is almost a universal finding [3,[10][11][12][13] , yet the extent of this risk varies considerably with differences in study design and geographic area. The initial reports were published by tertiary gastroenterology centers, thus the high risk detected might have been a consequence of referral bias and overinterpretation due to the high percentage of extensive and chronically active cases in these cohorts. Results of population-based studies are more reliable; however, several geographical and ethnic differences have been noted.The report of the meta-analysis by Eaden et al [3] in 2001 was one of several milestones in this subject. The incidence of UC-associated CRC was estimated based on 116 articles involving 54 478 patients in whom 1698 CRC cases were detected. This was a mixture of referral center-based, hospital-based, and population-based studies of variable methodological qualities and levels of detail. The reported incidence was higher in the US AbstractThe risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this chang...

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Evaluation of The Usefulness of Testing for P53 Mutations in Colorectal Cancer Surveillance for Ulcerative Colitis

Abstract: p53 Mutations 1) are associated with, and likely precede, dysplasia and cancer, 2) are associated with cancer-related mortality, and 3) may possibly be prevented by folic acid supplementation.

Cited by 97 publications

References 43 publications

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Predominant T helper type 2‐inflammatory responses promote murine colon cancers

Targeting activation-induced cytidine deaminase prevents colon cancer development despite persistent colonic inflammation

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

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