Abstract
Background
The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen ...criteria in centres from Eastern and Western European countries. The study aims at describing differences in incidence, treatment strategies, disease course and prognosis of ulcerative colitis (UC) Eastern and Western Europe.
Methods
UC patients were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations and medical treatment were captured throughout the follow-up period and entered in a validated web-database, www.epi-ibd.org. Associations between colectomy and covariates were analysed by multivariate Cox regression analyses.
Results
A total of 816 UC patients aged ≥15 years from 21 centres in 5 Eastern and 11 Western European countries were included. Overall, 51 (6%) patients underwent colectomy. A total of 190 (23%) patients were hospitalized at least once for their UC. Cancer was diagnosed in 28 (3%) patients, including 4 colorectal cancers. The use of medical therapy was comparable across Eastern and Western European centres (Table 1).
During follow-up, 121 out of 776 (16%) patients with limited UC (proctitis or left-sided colitis) progressed to extensive colitis. The median time to progression was 21 (IQR: 8-48) months from diagnosis. No patients from Eastern Europe were exposed to biological therapy prior to change in disease extent, compared to 6 out of 98 patients (6%) from Western Europe.
Multivariate Cox regression analysis showed no difference in risk of colectomy according to European region (Eastern vs. Western Europe, HR: 1.05, 95%CI: 0.48-2.29). Early intervention with biologicals (within 6 months) was associated with higher risk of colectomy (HR: 3.06, 95% CI: 1.23-7.58), and so was early introduction of immunomodulators (HR: 2.35, 95%CI: 1.16-4.76). Progression in disease extent to extensive colitis was significantly associated with higher risk of surgery (HR: 5.30, 95% CI: 2.36-11.90) and similarly extensive colitis at diagnosis compared to proctitis (HR: 3.48, 95% CI: 1.12-10.82).
Conclusion
After 10 years of follow up in this European multicentre study, only 6% percent had a colectomy performed. Despite the widespread use of immunomodulators and biologicals, 16% of patients with limited disease extent progressed to extensive colitis which was associated with higher risk of surgery. The need for early introduction of biological therapy and immunomodulators might predict risk of surgery.
Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC ...according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.
We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.
Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.
Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
German Research Foundation (DFG).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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