Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy

Alkhayyat, Motasem; Abureesh, Mohammad; Gill, Arshpal; Khoudari, George; Saleh, Mohannad Abou; Mansoor, Emad; Regueiro, Miguel

doi:10.1093/ibd/izaa252

Cited by 45 publications

(41 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the 2000s, anti-tumor necrosis factor therapy for rheumatoid arthritis was linked to an increased risk for infection and malignancy (Bongartz et al, 2006). However, those findings have been contradicted by evidence from recent studies: Use of anti-tumor necrosis factor therapy after an initial cancer diagnosis does not influence recurrence or new cancer (Waljee et al, 2020), and patients with inflammatory bowel disease who are treated with this therapy have lower rates of colorectal cancer (Alkhayyat et al, 2020). These findings altogether merit further study of relationship between immunosuppression and the risk for cancer.…”

Section: The Advent Of Cancer Immunotherapy Highlights the Complex Relationship Between Autoimmunity And Cancermentioning

confidence: 99%

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Chen

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. While autoimmunity has been suspected to be a risk factor for some cancers, the exact mechanisms underlying the connection between autoimmunity and cancer remain unclear and are often controversial. The link has been attributed to several mediators such as immune suppression, infection, diet, environment, or, perhaps most plausibly, chronic inflammation because of its well-recognized role in tumorigenesis. In that regard, autoimmune conditions are common causes of chronic inflammation and may trigger repetitive cycles of antigen-specific cell damage, tissue regeneration, and wound healing. Illustrating the connection between autoimmune diseases and cancer are patients who have an increased risk of cancer development associated with genetically predisposed insufficiency of cytotoxic T lymphocyte-associated protein 4 (CTLA4), a prototypical immune checkpoint against autoimmunity and one of the main targets of cancer immune therapy. The tumorigenic process triggered by CTLA4 insufficiency has been shown in a mouse model to be dependent on the type 2 cytokines interleukin-4 (IL4) and interleukin-13 (IL13). In this type 2 inflammatory milieu, crosstalk with type 2 immune cells may initiate epigenetic reprogramming of epithelial cells, leading to a metaplastic differentiation and eventually malignant transformation even in the absence of classical oncogenic mutations. Those findings complement a large body of evidence for type 1, type 3, or other inflammatory mediators in inflammatory tumorigenesis. This review addresses the potential of autoimmunity as a causal factor for tumorigenesis, the underlying inflammatory mechanisms that may vary depending on host-environment variations, and implications to cancer prevention and immunotherapy.

show abstract

Section: The Advent Of Cancer Immunotherapy Highlights the Complex Relationship Between Autoimmunity And Cancermentioning

confidence: 99%

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Chen

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In addition, SNOMED-CT allows for more concepts to be coded per clinical document compared to ICD making it more accurate in terms of documenting diagnoses and pertinent patient information. It is important to highlight that Explorys has been validated previously as a database (59) and in different specialties including gastroenterology (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)60,61).…”

Section: Discussionmentioning

confidence: 99%

“…To keep patients' information confidentiality, Explorys rounds cell counts to the nearest 10. Explorys database has been validated previously in multiple fields including surgery and gastroenterology (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Databasementioning

confidence: 99%

Epidemiology of gallbladder cancer in the Unites States: a population-based study

Alkhayyat¹,

Saleh²,

Qapaja³

et al. 2021

Chin Clin Oncol

Self Cite

View full text Add to dashboard Cite

Background: Gallbladder cancer (GBC) is the most common neoplasm of the biliary tract with the lowest rates of survival. Most GBCs are adenocarcinomas that arise from the epithelial lining of the gallbladder. There are limited data in the literature regarding the epidemiology of GBC. Using a large database, we aim to describe the epidemiology using a US population database. Methods: A multi-institutional database (Explorys Inc., Cleveland, OH, USA) was surveyed. A cohort of patients with a primary malignant neoplasm of gallbladder between 1999-2019 was identified. The prevalence rate was calculated and age-, race-, and sex-based distributions were described. Multivariate analysis was done to evaluate underlying associations. Results: Of the 56,197,690 individuals in the database, 4,790 individuals with GBC were identified with a prevalence rate of 8.5 per 100,000. Asian race has the highest prevalence of GBC (13.6/100,000). Patients with GBC were also more likely to be smokers, have a history of alcohol abuse, obesity, diabetes, cholelithiasis, chronic cholecystitis, primary sclerosing cholangitis (PSC), and chronic viral hepatitis. Conclusions: This is one of the largest US population studies to date evaluating the epidemiology of GBC. The 20-year period prevalence rate of GBC was 8.5 per 100,000. Patients with GBC were more likely to be elderly, females, obese, diabetic, and have chronic hepatobiliary disorders.

show abstract

“…However, we believe that medication exposure in our study was a proxy for underlying chronic inflammation rather than AN progression occurring as a result of the medication exposure itself. Recent studies have suggested that immunomodulator 31 and anti-TNF exposure 32 may in fact be associated with lower cancer risk, but it is uncertain as to whether this is indirectly a result of achieving inflammatory control and mucosal healing or a direct chemoprotective effect. Further prospective data are required to understand the long-term impact of medical therapy, particularly biological drugs, on CRC risk in IBD.…”

Section: Discussionmentioning

confidence: 99%

Multi-centre derivation and validation of a colitis-associated colorectal cancer risk prediction web-tool

Curtius

Kabir

Bakir

et al. 2020

Preprint

View full text Add to dashboard Cite

Background and Aims Ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN; high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in UC patients with LGD and create a visual web-tool to effectively communicate the risk. Methods In our retrospective multi-centre validated cohort study, adult UC patients with an index diagnosis of LGD, identified from four UK centres between 2001-2019, were followed until progression to AN. In the discovery cohort (n=248), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from 3 external centres (n=201). The validated model was embedded in a web-based tool to calculate and illustrate patient-specific risk. Results Four endoscopic variables were significantly associated with future AN progression in the discovery cohort: endoscopically visible LGD > 1 cm (HR = 2.8; 95% CI 1.3-6.0), incomplete endoscopic resection (HR = 2.9; 95% CI 1.3-6.5), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR = 3.0; 95% CI 1.3-6.7), and multifocality (HR = 2.8; 95% CI 1.3-6.1). In the validation cohort, this 4-variable model accurately predicted future AN cases with overall calibration Observed/Expected = 1 (95% CI 0.63-1.5), and achieved perfect specificity for the lowest predicted risk group over 13 years of follow-up. Conclusion Multi-cohort validation confirms that patients with large, unresected, and multifocal LGD and recent moderate/severe inflammation are at the highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator web-tool (www.UC-CaRE.uk) can be used to support treatment decision-making.

show abstract

Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy

Cited by 45 publications

References 58 publications

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Epidemiology of gallbladder cancer in the Unites States: a population-based study

Multi-centre derivation and validation of a colitis-associated colorectal cancer risk prediction web-tool

Contact Info

Product

Resources

About