Hereditary and inflammatory bowel disease related early onset colorectal cancer have unique characteristics and clinical course compared to sporadic disease

2021 ◽  
pp. cebp.0507.2021
Author(s):  
Arif A Arif ◽  
Daljeet Chahal ◽  
Gale K Ladua ◽  
Eric Bhang ◽  
Bill Salh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Clinical Course ◽  
Inflammatory Bowel ◽  
Sporadic Disease ◽  
Early Onset Colorectal Cancer

Clinical and molecular characterization of early-onset colorectal cancer patients with inflammatory bowel disease.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 689-689
Author(s):  
Alexandra Nicole Willauer ◽  
Jonathan M. Loree ◽  
Allan Andresson Lima Pereira ◽  
Michael Lam ◽  
Kanwal Pratap Singh Raghav ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Molecular Characterization ◽  
Bowel Disease ◽  
Early Onset ◽  
Kras Mutations ◽  
Pik3ca Mutations ◽  
Signet Ring ◽  
Inflammatory Bowel

689 Background: Recent reports suggest colorectal cancer incidence is steadily increasing in adults < 50 years old. This population has a number of unique pre-disposing conditions, such as inflammatory bowel disease (IBD), that may alter the disease biology within these patients. Methods: Using a cohort of 1876 patients with metastatic CRC (mCRC), we identified 622 patients aged < 50 years and reviewed their medical records for a diagnosis of IBD. Clinical, pathologic and overall survival (OS) were compared between patients with and without IBD in this age group. Results: Twenty of 622 (3.2%) early-onset mCRC patients had IBD. These patients were more likely to have mucinous or signet ring histologic features (50.0% vs 15.6%, OR 5.43, 95% CI 2.20-13.41, P < 0.0001) and less likely to have APC mutations (15.0% vs 42.7%, P = 0.019). A trend toward an increased prevalence of right-sided location (40.0% vs 24.1%, P = 0.053) and TP53 mutations (85.0% vs 65.1%, P = 0.091) and decreased prevalence of PIK3CA mutations (0.0% vs 15.5%, P = 0.057) and KRAS mutations (35.0% vs 50.0%, P = 0.11) were noted. There were no differences in prevalence of BRAF V600 (P = 0.99), CTNNB1 (P = 0.99), NRAS (P = 0.99), PTEN (P = 0.43), or SMAD4 (P = 0.75) mutations between patients with IBD and other early-onset mCRC. The presence of IBD in early-onset mCRC patients was associated with a worse OS compared to patients without IBD but who had mCRC (HR 1.82, 95% CI 0.90-3.69, P = 0.026). Conclusions: Early-onset mCRC patients with IBD are significantly more likely to have mucinous or signet ring histologic features and have fewer mutations in canonical CRC genes such as KRAS, PIK3CA, and APC. This suggests that this population likely develops through a unique molecular pathogenesis and they may respond differently to therapy. Further molecular characterization of this population is required.

scholarly journals COLORECTAL ADENOCARCINOMA DEVELOPING IN A YOUNG FEMALE WITH OVERLAP SYNDROME AND VERY EARLY ONSET-INFLAMMATORY BOWEL DISEASE: A CASE REPORT

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S14-S15
Author(s):  
Prashanthi Kandavel ◽  
Victoria Shakhin ◽  
Mallory Chavannes ◽  
Christopher Gayer ◽  
Hillel Naon ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Colorectal Adenocarcinoma ◽  
Clinical Course ◽  
Overlap Syndrome ◽  
High Risk Population ◽  
Endoscopic Screening ◽  
Inflammatory Bowel

Abstract We present a 4-year-old female diagnosed with very-early onset inflammatory bowel disease (VEO-IBD), ulcerative colitis type, and overlap syndrome based on clinical presentation, blood and stool studies, diagnostic endoscopies and liver biopsy. Her clinical course was complicated by pervasive psychological stressors, non-compliance with medical therapy, and frequent provider changes. Initial treatment included Prednisone, 6-mercaptopurine and Ursodiol. Treatment was escalated to include multiple biological agents which were stopped prematurely due to non-adherence. She developed weight loss and growth stunting, necessitating exclusive enteral nutrition and then parenteral nutrition. Due to medically refractory disease, she underwent a total colectomy with end ileostomy at the age of 13. Pathology revealed stage III colorectal adenocarcinoma (CRC) with lymph node involvement and transmural inflammation diagnostic of Crohn’s disease (CD). Genetic testing of the resected colon noted a missense mutation of TP53. Our patient completed 6 cycles of extensive and targeted chemotherapy with no evidence of disease reccurrence. She recently underwent ileal pouch-anal anastomosis and creation of a diverting ileostomy. CRC is exceedingly rare in pediatric IBD (PIBD) patients, with less than 30 reported cases in the available literature1. Most cases occurred in males and patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC), where the risk of developing CRC is four times greater2. The risk of CRC increases with disease duration, with most PIBD patients developing CRC at 25 years of age1. Interestingly, mutations in TP53, a tumour suppressor gene, have been found to occur more frequently in patients with IBD-CRC compared to those with sporadic-CRC or IBD without dysplasia3. Mutations in TP53 may not only increase a patients general susceptibility to CRC but may also accelerate its development by contributing to excessive inflammation4. Our patient’s treatment refractory clinical course and transition in IBD diagnosis from UC to CD highlights the complexity of VEO-IBD management. While rare in pediatric patients, the development of CRC is a life-threatening risk and it should be considered in patients with prolonged and severely refractory IBD with concomitant autoimmune liver disease. Our patient’s young age at the time of CRC diagnosis emphasizes the need for vigilant yearly endoscopic screening and development of pediatric guidelines for dysplasia monitoring in this high risk population. Further research is needed to evaluate the role of genetic variant screening in CRC risk stratification. References: 1. Aardoom MA, et al. Inflamm Bowel Dis. 2018;24(4):732–741. 2. Soetikno RM, et al. Gastrointest Endosc. 2002;56(1):48–54. 3. Yaeger R, et al. Gastroenterology. 2016;151(2):278–287. 4. Cooks T, et al. Cancer Cell. 2013;23(5):634–46.

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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