MP33-10 IDENTIFYING THE MECHANISTIC CONNECTION BETWEEN INFLAMMATORY BOWEL DISEASE AND PROSTATE CANCER: A LARGE-SCALE GENE EXPRESSION ANALYSIS

AbstractBackgroundInflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation.ObjectiveTo test the association between IBD with incident PC.Design, setting, and participantsWe studied 218,084 men in the population-based UK Biobank cohort, aged 40-69 at study entry between 2006 and 2010, with follow-up through mid-2015.Outcome measurements and statistical analysisWe assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of prostate cancer, and previous prostate-specific antigen testing.Results and limitationsMean age at study entry was 56 years, 94% of the men were white, and 1.1% (n=2,311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazards ratio [aHR] = 1.31, 95% Confidence interval [CI] = 1.03-1.67, p = 0.029). Separately analyzing the IBD subtypes of ulcerative colitis (UC) and Crohn’s disease (CD), the association with PC was only among men with the former (UC; aHR = 1.47, 95% CI = 1.11-1.95, p=0.0070), and not the latter (CD; aHR 1.06, 95% CI = 0.63-1.80, p = 0.82). Results are limited by lack of data on frequency of health care interactions.ConclusionsIn a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.Patient summaryThis study of over 200,000 men in the UK suggests that men with inflammatory bowel disease may be at a higher risk of prostate cancer than the general population.

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Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer

10.21236/ada453368 ◽

2006 ◽

Author(s):

Jonathan Rosenberg

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Hormone Refractory Prostate Cancer ◽

Hormone Refractory

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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0037 ◽

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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