Background:As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes. Methods:A cohort of 237 individuals were included from five countries: Crohn's disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region. Results:Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC >0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin. Conclusion:Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.

BackgroundColorectal cancer (CRC) is a significant health issue, with notable incidence rates in Norway. The immune response plays a dual role in CRC, offering both protective effects and promoting tumor growth. This research aims to provide a detailed screening of immune-related genes and identify specific genes in CRC and adenomatous polyps within the Norwegian population, potentially serving as detection biomarkers.MethodsThe study involved 69 patients (228 biopsies) undergoing colonoscopy, divided into CRC, adenomatous polyps, and control groups. We examined the expression of 579 immune genes through nCounter analysis emphasizing differential expression in tumor versus adjacent non-tumorous tissue and performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) across patient categories.ResultsKey findings include the elevated expression of CXCL1, CXCL2, IL1B, IL6, CXCL8 (IL8), PTGS2, and SPP1 in CRC tissues. Additionally, CXCL1, CXCL2, IL6, CXCL8, and PTGS2 showed significant expression changes in adenomatous polyps, suggesting their early involvement in carcinogenesis.ConclusionsThis study uncovers a distinctive immunological signature in colorectal neoplasia among Norwegians, highlighting CXCL1, CXCL2, IL1B, IL6, CXCL8, PTGS2, and SPP1 as potential CRC biomarkers. These findings warrant further research to confirm their role and explore their utility in non-invasive screening strategies.

We have previously identified increased levels of distinct bacterial taxa within mucosal biopsies from colorectal cancer (CRC) patients. Following prior research, the aim of this study was to investigate the detection of the same CRC‐associated bacteria in fecal samples and to evaluate the suitability of fecal samples as a non‐invasive material for the detection of CRC‐associated bacteria. Next‐generation sequencing (NGS) of the 16S ribosomal RNA (rRNA) V4 region was performed to evaluate the detection of the CRC‐associated bacteria in the fecal microbiota of cancer patients, patients with adenomatous polyp and healthy controls. Furthermore, 19 novel species‐specific quantitative PCR (qPCR) assays were established to detect the CRC‐associated bacteria. Approximately, 75% of the bacterial taxa identified in biopsies were reflected in fecal samples. NGS failed to detect low‐abundance CRC‐associated taxa in fecal samples, whereas qPCR exhibited high sensitivity and specificity in identifying all targeted taxa. Comparison of fecal microbial composition between the different patient groups showed enrichment of Fusobacterium nucleatum , Parvimonas micra , and Gemella morbillorum in cancer patients. Our findings suggest that low‐abundance mucosa‐associated bacteria can be detected in fecal samples using sensitive qPCR assays.

Accumulating evidence has related the gut microbiota to colorectal cancer (CRC). Fusobacterium nucleatum has repeatedly been linked to colorectal tumorigenesis. The aim of this study was to investigate microbial composition in different sampling sites, in order to profile the microbial dynamics with CRC progression. Further, we characterized the tumor-associated F. nucleatum subspecies. Here, we conducted Illumina Miseq next-generation sequencing of the 16S rRNA V4 region in biopsy samples, to investigate microbiota alterations in cancer patients, patients with adenomatous polyp, and healthy controls in Norway. Further, Fusobacterium positive tumor biopsies were subjected to MinION nanopore sequencing of Fusobacterium-specific amplicons to characterize the Fusobacterium species and subspecies. We found enrichment of oral biofilm-associated bacteria, Fusobacterium, Gemella, Parvimonas, Granulicatella, Leptotrichia, Peptostreptococcus, Campylobacter, Selenomonas, Porphyromonas, and Prevotella in cancer patients compared to adenomatous polyp patients and control patients. Higher abundance of amplicon sequence variants (ASVs) classified as Phascolarctobacterium, Bacteroides vulgatus, Bacteroides plebeius, Bacteroides eggerthii, Tyzzerella, Desulfovibrio, Frisingicoccus, Eubacterium coprostanoligenes group, and Lachnospiraceae were identified in cancer and adenomatous polyp patients compared to healthy controls. F. nucleatum ssp. animalis was the dominating subspecies. F. nucleatum ssp. nucleatum, F. nucleatum ssp. vincentii, Fusobacterium pseudoperiodonticum, Fusobacterium necrophorum, and Fusobacterium gonidiaformans were identified in five samples. Several biofilm-associated bacteria were enriched at multiple sites in cancer patients. Another group of bacteria was enriched in both cancer and polyps, suggesting that they may have a role in polyp development and possibly early stages of CRC.

Abstract Background One of the main drivers of colitis associated colorectal cancer (CA-CRC) is suspected to be long-standing mucosal inflammation, but far from all colitis patients develop cancer. We analyzed mucosal gene expression profiles in ulcerative colitis (UC) patients who have progressed to neoplasia (progressors) compared to those who have not (non-progressors) in order to identify underlying mechanisms for neoplastic progression in UC patients. Methods We performed transcriptome profiling on 143 mucosal samples from non-neoplastic colon segments of 14 UC progressors and 30 UC non-progressors from the prospective CA-CRC cohorts from Lovisenberg Diakonale- and Akershus University Hospitals in Norway. Differentially expressed genes were determined using SurePrint G3 human gene expression 60K microarray (Agilent Tech Inc.). Results 609 genes were differentially expressed between non-progressor- and progressor inflamed tissue, 24 genes between non-progressor- and progressor non-inflamed tissue, 404 genes between non-progressor non-inflamed- and -inflamed tissue and 26 genes between progressor non-inflamed- and inflamed tissue. In inflamed mucosa, genes related to metabolic processes such as xenobiotic- as well as carbohydrate and lipid metabolism were significantly higher expressed in progressors compared to non-progressors. Genes related to innate and adaptive immune responses were expressed at significantly lower levels. These main traits were not influenced by type of inflammation but apparent in both, chronic- and chronic active inflammation. However, chronic inflamed mucosa of progressors were also characterised by dysregulation of processes related to chromatin organization. Treatment with immunomodulators and biologics were equally distributed in the groups. Restriction of the analysis to patients without treatment of these drugs did not significantly influence the main results. In non-inflamed mucosa, the gene expression profile of progressors and non-progressors were remarkably similar. In fact, within the positively and negatively enriched gene ontologies, only the gene S100P was significantly deregulated with a higher expression in non-inflamed mucosa of the progressors. Conclusion Upregulated detoxification as well as dysregulated immune response and chromatin organization may be underlying processes for neoplastic progression in ulcerative colitis. Our findings warrant further evaluation.

Background: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naive patients and compared them to both symptomatic and healthy controls. Methods: Altogether, 323 subjects were included: Crohn's disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome. Results: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn's disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn's disease and ulcerative colitis (>2.6 normalized enrichment scores <-1.8). Gene expression signatures of Crohn's disease and ulcerative colitis did not predict time for treatment escalation (p = 0.175). No significant association was found between gene expression signatures and anti-TNF response. Conclusion: Non-inflamed samples are probably superior to inflamed samples when exploring gene expression signatures in IBD and might reveal underlying mechanisms central for disease initiation. The gene expression signatures of the control groups were related to if they were symptomatic or not, which may have important implications for future study designs.

BACKGROUND AND AIM:Modern treatment strategies for inflammatory bowel disease (IBD) are postulated to change the natural disease course. Inception cohort studies are the gold standard for investigating such changes. We have initiated a new population-based inception cohort study; Inflammatory bowel disease in South Eastern Norway III (IBSEN III). In this article, we describe the study protocol and baseline characteristics of the cohort.METHODS:IBSEN III is an ongoing, population-based observational inception cohort study with prospective follow-up. Adult and pediatric patients with suspected IBD in the South-Eastern Health Region of Norway (catchment area of 2.95 million inhabitants in 2017), during the 3-year period from 2017 to 2019, were eligible for inclusion. Comprehensive clinical, biochemical, endoscopic, demographic, and patient-reported data were collected at the time of diagnosis and throughout standardized follow-up. For a portion of the patients, extensive biological material was biobanked.RESULTS:The study included 2168 patients, of whom 1779 were diagnosed with IBD (Crohn's disease: 626, ulcerative colitis: 1082, IBD unclassified: 71). In 124 patients, there were subtle findings indicative of, but not diagnostic for, IBD. The remaining 265 patients were classified as symptomatic non-IBD controls.CONCLUSION:We have included patients in a comprehensive population-based IBD cohort from a catchment population of 2.95 million, and a unique biobank with materials from newly diagnosed and treatment-naïve IBD patients and symptomatic non-IBD controls. We believe this cohort will add important knowledge about IBD in the years to come.

Objective The association between ulcerative colitis (UC) and colorectal cancer (CRC) is widely accepted, although attenuated risk has been reported in recent years. Colonoscopic surveillance is recommended with intervals based on established clinical risk factors. Nevertheless, a significant number of patients develop interval cancers, indicating the need of improved individualised assessment. In the present study, we evaluated clinical risk factors associated with CRC during a prescheduled follow-up 20 years after diagnosis, the IBSEN study. Design A population-based inception cohort of patients diagnosed with inflammatory bowel disease from 1 January 1990 until 31 December 1993, prospectively followed at 1, 5, 10 and 20 years after diagnosis. A total of 517 patients with UC were included; 264 (51 %) men; median age at inclusion 37.4 years (4–88). Results The overall incidence of CRC was 1.6% (8/517) at a 20-year follow-up. The total lifetime risk of CRC prior to or after UC diagnosis was 2.3%. (12/517). Patients older than 70 years at diagnosis had a 15-fold higher risk of CRC compared with those diagnosed when younger than 40 years, with HR 15.68 (95% CI: 1.31 to 187.92). Neither sex, first-degree relative with CRC, extent of colitis nor primary sclerosing cholangitis affected the risk of CRC. Conclusion The risk of CRC in UC was low and comparable with the risk of CRC in the background population of Norway.

Introduction: Patients with coeliac disease commonly report symptoms of brain fog'. The aim of this study was to assess self-reported symptoms of impaired concentration in coeliac disease before and after treatment with gluten-free diet, compared with healthy controls and patient controls.Methods: Patients with newly diagnosed coeliac disease were included consecutively from two out-patient clinics. The patients completed the questionnaires Adult ADHD Self-Report Scale v1.1 Symptoms Checklist (ASRS), Hospital Anxiety and Depression Scale (HADS) and Gastrointestinal Symptom Rating Scale (GSRS) prior to start of a gluten-free diet and after at least 12 months on the diet. Patients with an established diagnosis of inflammatory bowel disease served as patient controls (n=36). Health care personnel at Oslo University Hospital served as healthy controls (n=60) and filled out ASRS and HADS.Results: A total of 31 newly diagnosed coeliac patients were included in the study. Of these, 26 patients met for follow-up and repeated the questionnaires. Prior to treatment, patients with coeliac disease had significantly higher scores than healthy controls on both the ASRS (p=.0014) and HADS (p=.0004). After a gluten-free diet, their scores improved and were not significantly different from healthy controls. There were no significant differences between patients with coeliac disease prior to treatment and patient controls with inflammatory bowel disease.Conclusion: Prior to treatment, coeliac disease patients reported significantly more symptoms than healthy controls on ASRS and HADS. The differences disappeared after a minimum of 12 months on a gluten-free diet.

AIM To evaluate the use of chromoendoscopy for surveillance of ulcerative colitis in a real-life community hospital setting. METHODS Patients with extensive ulcerative colitis, having disease duration of more than 8 years and who presented between the years of 1999 to 2013, were offered enrolment in this single cohort prospective study. All participants underwent standard bowel preparation with sodium phosphate and chromoendoscopy. Two expert endoscopists, novice to chromoendoscopy, evaluated each segment of the colon with standard-definition colonoscopes after spray application of 0.4% indigo carmine. All observed lesions were recorded and evaluated before being removed and/or biopsied. In addition, nontargeted biopsies were taken from each segment of the colon. The dysplasia detection rate and dysplasia detection yield were ascertained. RESULTS A total of 21 neoplastic lesions (2 carcinomas, 4 of high-grade dysplasia and 15 of low-grade dysplasia) and 27 nondysplastic lesions were detected in 16 of the total 67 patients (70% male; median disease duration: 17 years; median age at diagnosis: 25 years; 92% aminosalicylate-treated). The dysplasia detection rate was 10.5% (7/67 patients). The dysplasia detection yield was 20.8% (10/48) for targeted biopsies and 3.5% (11/318) for nontargeted biopsies. The sensitivity and specificity for the macroscopic evaluation of neoplasia using chromoendoscopy were 48% [95% confidence interval (CI): 26%-70%] and 96% (95% CI: 93%-98%), respectively. The positive predictive and negative predictive values were 42% (95% CI: 27%-59%) and 97% (95% CI: 95%-98%), respectively. A total of 19/21 dysplastic lesions were detected in mucosa with histologic inflammation. CONCLUSION Chromoendoscopy seems to be of value for dysplasia surveillance of ulcerative colitis in a community hospital setting. The yield of non-targeted biopsies is negligible.

Abstract Background and aim: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD. Material and methods: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and β-actin by a laboratory blinded to clinical data. Results: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16–100%) for CRC and 33% (95% CI 13–61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81–91%) and 93% (95% CI 88–96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93–99%) and was 28 (95% CI 22–34%) to detect any colorectal neoplasia (CRN). Conclusion: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. METHODS: We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. RESULTS: Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied. CONCLUSIONS: In an analysis of stool samples from 3 independent studies of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance.

Introduction: First-degree relatives (FDR) of patients with colorectal cancer (CRC) have been shown to have a 2-to 3-fold increased risk of developing CRC compared with the overall population.It is likely that CRC susceptibility in these individuals results from common variants in low-penetrance genes.Very little is known about the relevance of genetic variants in the development of colorectal adenomas according to the family history of CRC.Trying to address this issue we carried out a case-control study comprising 750 FDR of patients with nonsyndromic CRC (cases), and 750 sex-aged-and histological lesion-matched individuals with no family history of CRC (controls).We aimed to evaluate the role of certain SNPs associated with CRC risk in the development of adenomas and family history of CRC.Methods: Cases and controls were selected from the Spanish CRC screening registries in Aragon and The Canary Islands.All subjects underwent at least one colonoscopy and diagnosis was confirmed by histological study.Genomic DNA from participants was genotyped by the MassArray™(Sequenom) platform for a panel of 99 SNPs previously associated with CRC risk.Results: Average age of participants was 54.5 +/-9.4 years with a slight predominance of women (51.7%).In 57% of patients, no preneoplastic lesions were found.By contrast, 288 patients (144 cases,144 controls) showed non advanced adenomas(NAA), and 354 patients (177cases,177controls) had advanced adenomas(AA).Concerning gene analysis, 2SNPs (rs10505477, rs6983267) located in the gen CASC8 were associated with the development of adenomas.Thus, the rs10505477G and the rs6983267T alleles were significantly associated with a reduced risk of adenomas in controls (log-additive models, OR:0.67, 95%CI:0.54-0.83,and OR:0.66, 95%CI:0.54-0.84,respectively).However, such a protective effect was not observed in cases.In the stratified analysis by histological lesion, the rs10505477G and the rs6983267T variants were significantly associated with a reduced risk of both, NAA and AA in controls, although this effect was stronger on the risk of developing NAA (OR:0.63,95%CI:0.47-0.84 for rs10505477, and OR:0.64, 95%CI:0.47-0.86 for rs6983267).Finally, 2 SNPs (rs10795668, rs11255841) located in the non-coding LINC00709 gene were significantly associated with a reduced risk of NAA in both, cases (recessive models, OR:0.22,95%CI:0.06-0.72 for rs10795668, and OR:0.08, 95%CI:0.03-0.61for rs11255841) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75 for rs10795668G, and OR:0.52, 95%CI:0.35-0.78 for rs11255841), suggesting their possible implication in early stages of CRC development.Conclusions: Family history of CRC and some specific variants associated with CRC risk (rs10505477, rs6983267, rs10795668, and rs11255841) are involved in the development of colorectal adenomas or specific histological subtypes.

The knowledge about correlation patterns between the fecal microbiota and inflammatory bowel diseases (IBD)-comprising the two subforms Crohn's disease (CD) and ulcerative colitis (UC)-for newly diagnosed untreated children is limited. To address this knowledge gap, a selection of faecal specimens (CD, n = 27 and UC, n = 16) and non-IBD controls (n = 30) children (age < 18 years) was analysed utilising bacterial small subunit (SSU) rRNA. We found, surprising age dependence for the fecal microbiota correlating to IBD. The most pronounced patterns were that E. coli was positively (R-2 = 0.16, P = 0.05) and Bacteroidetes, negatively (R-2 = 0.15, P = 0.05) correlated to age for CD patients. For UC, we found an apparent opposite age-related disease correlation for both Bacteroides and Escherichia. In addition, there was an overrepresentation of Haemophilus for the UC children. From our, results we propose a model where the aetiology of IBD is related to an on-going immunological development in children requiring different age-dependent bacterial stimuli. The impact of our findings could be a better age stratification for understanding and treating IBD in children.

Our knowledge about the microbiota associated with the onset of IBD is limited. The aim of our study was to investigate the correlation between IBD and the fecal microbiota for early diagnosed untreated patients. The fecal samples used were a part of the Inflammatory Bowel South-Eastern Norway II (IBSEN II) study and were collected from CD patients (n=30), UC patients (n=33), unclassified IBD (IBDU) patients (n=3), and from a control group (n=34). The bacteria associated with the fecal samples were analyzed using a direct 16S rRNA gene-sequencing approach combined with a multivariate curve resolution (MCR) analysis. In addition, a 16S rRNA gene clone library was prepared for the construction of bacteria-specific gene-targeted single nucleotide primer extension (SNuPE) probes. The MCR analysis resulted in the recovery of five pure components of the dominant bacteria present: Escherichia/Shigella, Faecalibacterium, Bacteroides, and two components of unclassified Clostridiales. Escherichia/Shigella was found to be significantly increased in CD patients compared to control subjects, and Faecalibacterium was found to be significantly reduced in CD patients compared to both UC patients and control subjects. Furthermore, a SNuPE probe specific for Escherichia/Shigella showed a significant overrepresentation of Escherichia/Shigella in CD patients compared to control subjects. In conclusion, samples from CD patients exhibited an increase in Escherichia/Shigella and a decrease in Faecalibacterium indicating that the onset of the disease is associated with an increase in proinflammatory and a decrease in anti-inflammatory bacteria.

3607 Background: Surveillance for colorectal cancer (CRC) in inflammatory bowel disease (IBD) has so far not been effective. Mucosal or fecal biomarkers may be useful in the selection of high risk patients. The yield may depend on the underlying carcinogenic pathway. In IBD associated CRC (IBD-CRC) the distribution of chromosomal instability (CIN) and microsatellite instability (MSI) is not well documented. Our objective was to determine the distribution of CIN and MSI and the association to clinico-histological factors in a cohort of patients with IBD-CRC. Methods: Ploidy was measured by high-resolution image cytometry and MSI by using two markers (BAT 25 and BAT26) in 62 patients with 72 CRC-IBD selected by matching the Norwegian Cancer Registry with IBD cohorts of three university hospitals in Oslo. The association between ploidy/MSI status and clinicohistological factors were analyzed by non-parametric tests. Results: Ploidy status was analyzed in 67 (93%), microsatellite stability in 68 (94%) tumors. Fourty-nine (73.1%) were non-diploid (43 aneuploid, 1 polyploid, 5 tetraploid), 13 (19.4 %) diploid, five (7.5%) indeterminate. Forty-three (63.2%) were microsatellite stable (MSS), four (5.8%) microsatellite instable (MSI). One tumor was MSI in BAT25 but MSS in BAT26. Twenty (29.5%) tumors showed no PCR-product in at least one of the markers. In 46 tumors, both ploidy and MSI status were available. All non-diploid tumours (36, 78.3%) were MSS and all MSI tumors (4, 8.7%) were diploid. Six (13%) tumors were diploid and MSS. Four patients were treated with 5-ASA prior to diagnosis of CRC. Three developed diploid, one aneuploid cancers. Of the untreated patients, 31 developed aneuploid, 7 diploid cancers (p=0.036). We did not find an association between age, gender, type of IBD, duration of IBD, localisation of CRC,TNM-stage and CIN or MSI. Conclusions: The majority of CRC-IBD in our cohort seem to present CIN and only a minority MSI. Some CRC-IBD patients present neither CIN nor MSI. Future studies should determine whether these display the CpG island methylator phenotype. Biomarkers for CRC-IBD should be derived from all three pathways.

Tap-water has recently been identified as an important epidemiological parameter in inflammatory bowel disease (IBD). Whether bacteria present in tap-water are involved in IBD still remains unknown. To address this question, the dominant microbiota in tap-water samples from households of patients with IBD, and from those of non-IBD control patients, were screened. Tap-water from both pediatric patients (<18 years) and adults with ulcerative colitis (UC), Crohn's disease (CD) and IBD unclassified (IBDU) were sampled in the south-eastern part of Norway. A total of 145 patients diagnosed during 2005-2007 were included in the study.

An alternative transcript variant of SLC39A14, caused by pre-mRNA splicing, was recently suggested as a biomarker for colorectal cancer (CRC). In our study, we have validated the cancer-specific splicing pattern of the mutually exclusive exons 4A and 4B in altogether 244 colorectal tissue samples. Exon-specific quantitative RT-PCR analyses across 136 Stage IIV CRC samples and 44 normal colonic mucosa samples showed complete cancer-specificity, as well as 94% sensitivity of SLC39A14-exon4B relative to SLC39A14-exon4A expression. However, across 20 samples from a range of healthy tissues, 18 expressed the CRC variant. This was true also for ten benign lymph nodes, demonstrating that the cancer-specificity is mainly confined to the colon and rectum. Hence, clinical use of SLC39A14-exon4B as a detection marker for CRC other than in samples taken from the bowel wall is diminished. Prognostic value by detection of metastasis to lymph nodes is also abated, elucidating an important pitfall to biomarker discovery. However, analyses of ten nondysplastic biopsies from patients with active inflammatory bowel disease showed negative results in seven samples and only weakly positive results in three samples, suggesting value of SLC39A14-exon4B as a marker to distinguish CRC from other pathologic conditions of the colon. In conclusion, the SLC39A14-exon4B transcript variant is a CRC biomarker with high sensitivity and organ-confined specificity. Further use of the transcript and its encoded protein isoform should be explored in an organ-confined context.