Association Between Reduced Plasma 25-Hydroxyvitamin D and Increased Risk of Cancer in Patients With Inflammatory Bowel Disease

2015 ◽  
Vol 13 (4) ◽  
pp. 813-814 ◽  
Author(s):  
Matthew T. Kitson ◽  
Mayur Garg ◽  
Stuart K. Roberts
1995 ◽  
Vol 9 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Anders M Ekbom

There is an increased risk of cancer in both ulcerative colitis and Crohn's disease. In 3121 patients with ulcerative colitis, 225 cases of cancer were diagnosed compared with 142.1 expected (standardized incidence ratio [SIR] 1.6, 95% CI 1.4 to 1.8), and in 1655 patients with Crohn's disease, 58 cases of cancer were detected compared with 47.1 expected (SIR 1.2, 95% CI 0.9 to 1.6). After excluding colorectal cancer the observed number of malignancies was very close to that expected for ulcerative colitis (SIR 1.0, 95% CI 0.9 to 1.2) and for Crohn's disease (SIR 1.1, 95% CI 0.8 to 1.5). Thus, the increased risk of cancer in inflammatory bowel disease is confined to colorectal cancer. In Crohn's disease 12 cases of colorectal cancer were observed (SIR 2.5, 95% CI 1.3 to 4.3). The increased risk was confined to those with colonic involvement and young age at diagnosis. In patients with colonic involvement and younger than age 30 years at diagnosis, the SIR was 20.9 (95% CI 6.8 to 48.7) versus 2.2 for those older than 30 years at diagnosis (95% CI 0.6 to 5.7). In ulcerative colitis 91 cases of colorectal cancer were observed with an SIR of 5.7 (95% CI 4.6 to 7.0). Extensive disease and young age at diagnosis were independent risk factors. Pancolitis at diagnosis resulted in an SIR of 14.8 (95% CI 11.4 to 18.9), 2.8 in left-sided colitis (95% CI 1.6 to 4.4) and 1.7 in proctitis (95% CI 0.8 to 3.2). There is great variation in the risk estimates in different studies worldwide. Different treatment strategies could be an explanation, a hypothesis that was substantiated in a study of 102 cases of colorectal cancer among patients with ulcerative colitis compared with 196 controls. Pharmacological therapy with sulfasalazine entailed a strong protective effect against colorectal cancer (relative risk of 0.34, 95% CI 0.190 to 0.62).


Author(s):  
Vanessa Zaiatz Bittencourt ◽  
Fiona Jones ◽  
Miriam Tosetto ◽  
Glen A Doherty ◽  
Elizabeth J Ryan

Abstract Background and aims Inflammatory Bowel Disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic conditions characterized by severe dysregulation of innate and adaptive immunity resulting in the destruction of the intestinal mucosa. Natural Killer (NK) cells play a pivotal role in the dynamic interaction between the innate and adaptive immune response. There is an increasing appreciation for the key role immunometabolism plays in the regulation of NK cell function, yet little remains known about the metabolic profile, cytokine secretion and killing capacity of human NK cells during active IBD. Methods PBMC were isolated from peripheral blood of patients with moderate to severely active IBD and healthy controls. NK cells were stained with a combination of cell surface receptors, intracellular cytokines, proteins and analyzed by flow cytometry. For measurements of NK cell cytotoxicity, the calcein-AM release assay was performed. Metabolic profile was analyzed by extracellular flux analyzer. Results NK cells from IBD patients produce large quantities of pro-inflammatory cytokines, IL-17A and TNF-α ex vivo but have limited killing capability. Furthermore, patient NK cells have reduced mitochondrial mass and oxidative phosphorylation. mTORC1, an important cell and metabolic regulator, demonstrated limited activity in both freshly isolated cells and cytokine stimulated cells. Conclusions Our results demonstrate that circulating NK cells of IBD patients have an unbalanced metabolic profile, with faulty mitochondria and reduced capacity to kill. These aberrations in NK cell metabolism may contribute to defective killing and thus the secondary infections and increased risk of cancer observed in IBD patients.


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