P071 Risk Factors Associated With Small Bowel Adenocarcinoma in Crohn's Disease: A Case-Control Study

Piton, Gaël; Cosnes, Jacques; Monnet, Élisabeth; Beaugerie, Laurent; Cadiot, Guillaume; Flourié, Bernard; Lémann, M.; Colombel, J.-F.; Marteau, P.; Carbonnel, F.

doi:10.1016/s1873-9954(07)70083-6

Cited by 8 publications

(8 citation statements)

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“…Small bowel adenocarcinoma and colorectal cancer show overlaps in morphology and hereditary and non-hereditary risk factors, including the hereditary non-polyposis colorectal cancer syndrome, familial adenomatous polyposis, and Crohn's disease. [2][3][4] Recent studies, however, provide evidence for a somewhat different molecular pathogenesis of the majority of sporadic carcinomas in both locations. [5][6][7][8][9] Microsatellite and chromosomal instability (MSI and CIN) are two divergent types of genomic instability found in adenocarcinomas throughout the gastrointestinal tract, including the small intestine.…”

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Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

et al. 2011

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Characterization of tumor genetics and epigenetics allows to stratify a tumor entity according to molecular pathways and may shed light on the interactions of different types of DNA alterations during tumorigenesis. Small intestinal adenocarcinoma is rare, and to date the interrelation of genomic instability and epigenetics has not been investigated in this tumor type. We therefore analyzed 37 primary small bowel carcinomas with known microsatellite instability and KRAS status for chromosomal instability using comparative genomic hybridization, for the presence of aberrant methylation (CpG island methylation phenotype) by methylation-specific polymerase chain reaction, and for BRAF mutations. Chromosomal instability was detected in 22 of 37 (59%) tumors (3 of 9 microsatellite instable, and 19 of 28 microsatellite stable carcinomas). Nine carcinomas (24%) were microsatellite and chromosomally stable. High-level DNA methylation was found in 16% of chromosomal instable tumors and in 44% of both microsatellite instable and microsatellite and chromosomally stable carcinomas. KRAS was mutated in 55, 0, and 10% of chromosomal instable, microsatellite instable, and microsatellite and chromosomally stable tumors, respectively whereas the frequencies of BRAF mutations were 6% for chromosomal instable and 22% for both microsatellite instable and microsatellite and chromosomally stable carcinomas. In conclusion, in this study we show that chromosomal instable carcinomas of the small intestine are distinguished from microsatellite instable and microsatellite and chromosomally stable tumors by a high frequency of KRAS mutations, low frequencies of CpG island methylation phenotype, and BRAF mutations. In microsatellite instable and microsatellite and chromosomally stable cancers, CpG island methylation phenotype and BRAF/KRAS mutations are similarly distributed, indicating common mechanisms of tumor initiation or progression in their molecular pathogenesis.

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Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

et al. 2011

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“…The risk of developing small bowel carcinoma was also found to be much higher in patients whose disease was confined to the small bowel than in the patients with ileocolic CD [9] . Protective factors against the development of small bowel carcinoma in CD have been less frequently studied, but it has been proposed that small bowel resection and prolonged use of salicylates may be protective [10] . In our case, the only identified risk factor was the location of CD, confined to the small bowel.…”

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confidence: 99%

Signet Ring Cell Carcinoma, Ileal Crohn Disease or Both - A Case of Diagnostic Challenge

Carvalho¹,

Tavares²,

Goulart³

et al. 2017

GE Port J Gastroenterol

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ResumoO carcinoma de células em anel de sinete é uma forma rara de adenocarcinoma que afeta predominantemente o estômago. A forma primária do íleon é muito rara e apresenta mau prognóstico. Apresentamos um caso de doença de Crohn do íleon cuja forma de apresentação cursou com quadro oclusivo associado a adenocarcinoma de cé-lulas em anel de sinete do íleon. A doente apresentava história prévia de diarreia crónica e tinha história familiar de doença inflamatória. Foi submetida a ressecção cirúr-gica e os achados histopatológicos revelaram a presença de aspetos compatíveis com doença de Crohn do íleon e adenocarcinoma de células em anel de sinete. Foi proposta uma associação com esta forma rara de tumor e infla- Keywords Signet ring cell carcinoma · Crohn disease · Ileum AbstractSignet ring cell carcinoma is a rare form of adenocarcinoma that predominantly affects the stomach. Signet ring cell carcinoma originated from the ileum is extremely rare and the prognosis is poor. We present a case of small bowel obstruction with features suggesting Crohn disease of the ileum. The symptoms were chronic diarrhea and abdominal pain with a family history of inflammatory bowel disease. The patient underwent surgery and histopathology revealed both aspects of signet ring cell carcinoma and Crohn disease of the ileum. An association between long-standing inflammation and the development of this subtype of tumor has been proposed but there are no established surveillance guidelines for small bowel neoplasm in inflammatory bowel disease. 48 mação de longa duração, contudo, não existem recomendações estabelecidas de vigilância de neoplasia na doença inflamatória intestinal com atingimento ileal.

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“…Apart from CD and Crohns's disease, FAP and HNPCC are well-established risk factors (28)(29)(30). Young age of onset and detection of MSI are typical for the development of SBA in the setting of HNPCC.…”

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confidence: 99%

Small bowel adenocarcinomas in celiac disease follow the CIM-MSI pathway

et al. 2010

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Abstract. Celiac disease (CD) is an inflammatory disorder associated with an increased risk of small bowel adenocarcinoma. Recent studies have demonstrated aberrant CpG island methylation (CIM) in chronic inflammation, aging and cancer. We hypothesized that CIM may link CD to small bowel carcinogenesis. We determined microsatellite instability (MSI), CIM, and expression of MLH1 and MGMT in 3 CDassociated small bowel carcinomas and corresponding nonneoplastic mucosa. The results were compared to those of small bowel mucosa from CD patients without carcinoma and 20 small bowel carcinomas from a non-CD origin. A high level CIM/MSI phenotype was found in all of the 3 CDassociated carcinomas and was associated with loss of MLH1 expression due to hypermethylation of the MLH1 promoter. This phenotype was noted in only 2 of the 20 investigated non-CD-associated carcinomas. Low-level CIM was already detectable in 9 of the 12 non-neoplastic mucosa samples of CD patients and in non-CD-associated carcinomas of elderly patients. In conclusion, our data reveal that the high-level CIM/MSI pathway is typical of CD-associated small bowel carcinomas and indicate that aberrant CpG island methylation links CD and carcinogenesis. The data further suggest that CD should be considered in patients with small bowel adenocarcinoma, particularly when the tumors display MSI.

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P071 Risk Factors Associated With Small Bowel Adenocarcinoma in Crohn's Disease: A Case-Control Study

Cited by 8 publications

References 0 publications

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP

Signet Ring Cell Carcinoma, Ileal Crohn Disease or Both - A Case of Diagnostic Challenge

Small bowel adenocarcinomas in celiac disease follow the CIM-MSI pathway

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