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Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy.

ABSTRACT: The cancer risk of patients with inflammatory bowel diseases (IBD) has not been well documented in southern Europe. This study aimed to evaluate the overall pattern of cancer risk among patients with IBD in Friuli Venezia Giulia, northeastern Italy. A population-based cohort study was performed through a record linkage between local healthcare databases and the cancer registry (1995-2013). We identified 3664 IBD patients aged 18-84 years, including 2358 with ulcerative colitis (UC) and 1306 with Crohn's disease (CD). Sex- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were used to compare the cancer incidence of IBD patients with the general population. The cumulative cancer risk among IBD patients reached about 10% after 10 years of follow-up. A total of 246 cancers occurred among UC patients (SIR = 1.05, 95% CI: 0.92-1.19), and 141 among CD patients (SIR = 1.20, 95% CI: 1.01-1.41). As compared with the general population, no increased risk of colorectal cancers was observed for either UC or CD patients, whereas the risk of anal cancer was significantly elevated among UC patients (SIR = 6.03, 95% CI: 1.24-17.60). Increased risks were seen for specific extra-intestinal cancers, including corpus uteri (SIR = 2.67, 95% CI: 1.07-5.50) and kidney (SIR = 2.06, 95% CI: 1.03-3.69) among UC patients; thyroid (SIR = 5.58, 95% CI: 2.41-11.00) and skin non-melanoma (SIR = 1.86, 95% CI: 1.32-2.55) among CD patients. This population-based study showed that both UC and CD patients had a colorectal cancer risk similar to that of the general population. However, they were at a higher risk of developing certain extra-intestinal cancer types. Although detection biases cannot be excluded, the study findings pointed to a role of long-standing exposures to immunosuppressive therapies, underlying disease status, as well as the interactions with lifestyle factors. Our findings lent additional support to the need for monitoring the cancer burden in this at-risk population.

SUBMITTER: Taborelli M

PROVIDER: S-EPMC7310697 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy.

Taborelli Martina M Sozzi Michele M Del Zotto Stefania S Toffolutti Federica F Montico Marcella M Zanier Loris L Serraino Diego D

PloS one 20200623 6

The cancer risk of patients with inflammatory bowel diseases (IBD) has not been well documented in southern Europe. This study aimed to evaluate the overall pattern of cancer risk among patients with IBD in Friuli Venezia Giulia, northeastern Italy. A population-based cohort study was performed through a record linkage between local healthcare databases and the cancer registry (1995-2013). We identified 3664 IBD patients aged 18-84 years, including 2358 with ulcerative colitis (UC) and 1306 with ...[more]

PMID: 32574216

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Project description:Background & aimsThe incidence of inflammatory bowel diseases (IBDs) in older adults is increasing. We performed a systematic review and meta-analysis to evaluate progression of elderly onset (EO) IBD in population-based cohorts and compared it with adult onset (AO) IBD.MethodsIn a systematic review through June 1, 2019, we identified population-based cohort studies of EO IBD reporting the cumulative risk of hospitalization, surgery, mortality, treatment patterns, escalation, and/or malignancy. Data were synthesized using random-effects meta-analysis as cumulative risk of events at 1 year, 5 years, and 10 years, and compared with data from patients with AO IBD in the same cohorts.ResultsWe identified 9 studies, comprising 14,765 patients with EO IBD. In patients with EO Crohn's disease (CD), the cumulative 5-year risk of surgery was 22.6% (95% CI, 18.7-27.2) and was similar to that of patients with AO CD (relative risk [RR], 1.04; 95% CI, 0.80-1.34). Overall exposure to corticosteroids was comparable between patients with EO CD vs AO CD (5-year risk: 55.4%; 95% CI, 53.4-57.4; RR, 0.88; 95% CI, 0.78-1.00), but exposure to immunomodulators (31.5%; 95% CI, 29.7-33.4; RR, 0.62; 95% CI, 0.51-0.77) or biologic agents (6.5%; 95% CI, 5.6-7.6; RR, 0.36; 95% CI, 0.25-0.52) was significantly lower for patients with EO CD than for patients with AO CD. Similarly, in patients with EO ulcerative colitis (UC), the cumulative 5-year risk of surgery was 7.8% (95% CI, 5.0-12.0), similar to the risk for patients with AO UC (RR, 1.29; 95% CI, 0.79-2.11). Overall exposure to corticosteroids was comparable between patients with EO UC vs AO UC (5-year risk: 57.2%; 95% CI, 55.6-58.7; RR, 0.98; 95% CI, 0.91-1.06), but exposure to immunomodulators (16.1%; 95% CI, 15.0-17.2; RR, 0.58; 95% CI, 0.54-0.62) or biologic agents (2.0%; 95% CI, 1.6-2.5; RR, 0.36; 95% CI, 0.24-0.52) was significantly lower for patients with EO UC than for patients with AO UC. Patients with EO IBD appeared to have increased mortality, but not malignancy, compared with the general population. There were few data on comorbidities or adverse effects of medications.ConclusionsIn a systematic review and meta-analysis, we found that patients with EO IBD have a similar risk of surgery as patients with AO IBD. However, patients with EO IBD are less likely to receive treatment with immunomodulators or biologic agents.

Project description:In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD.

Dataset Information

Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy.

Publications

Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy.

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