DNA Damage and Oxidative DNA Damage in Inflammatory Bowel Disease.
OBJECTIVE
Inflammation has long been regarded as a major contributor to cellular oxidative damage and to be involved in the promotion of carcinogenesis.


METHODS
We aimed to investigate the oxidative damage in inflammatory bowel disease [IBD] patients through a case-control and prospective study involving 344 IBD patients and 294 healthy controls. DNA damage and oxidative DNA damage were measured by comet assay techniques, and oxidative stress by plasmatic lipid peroxidation, protein carbonyls, and total antioxidant capacity.


RESULTS
Higher DNA damage [p < 0.001] was found both in Crohn's disease [CD] (9.7 arbitrary units [AU]; interquartile range [IQR]: 6.2-14.0) and ulcerative colitis [UC] [7.1 AU; IQR: 4.4-11.7], when compared with controls [5.4 AU; IQR: 3.8-6.8], and this was also the case with oxidative DNA damage [p < 0.001] [CD: 3.6 AU; IQR: 1.8-6.8; UC: 4.6 AU; IQR: 2.4-8.1], when compared with controls: 2.3 AU; IQR: 1.2-4.2]. Stratifying patients into groups according to therapy (5-aminosalicylic acid [5-ASA], azathioprine, anti-TNF, and combined therapy [azathioprine and anti-TNF]) revealed significant between-group differences in the level of DNA damage, both in CD and UC, with the combined therapy exhibiting the highest DNA damage levels [11.6 AU; IQR: 9.5-14.3, and 12.4 AU; IQR: 10.6-15.0, respectively]. Among CD patients, disease behaviour [B1 and B2], and age at diagnosis over 40 years [A3] stand as risk factors for DNA damage. For UC patients, the risk factors found for DNA damage were disease activity, treatment, age at diagnosis under 40 years [A1 + A2] and disease locations [E2 and E3].


CONCLUSIONS
In IBD there is an increase in DNA damage, and treatment, age at diagnosis and inflammatory burden seem to be risk factors.
National Institute of Health - Environmental Health Department, Oporto, Portugal.|MedInUP - Centre for Drug Discovery and Innovative Medicines, University of Oporto, Oporto, Portugal.|EPIUnit - Institute of Public Health, University of Oporto, Oporto, Portugal.
Cristiana
C
Pereira
Gastroenterology Department, Faculty of Medicine, Centro Hospitalar São João, Oporto, Portugal.
Rosa
R
Coelho
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Oporto, Portugal.
Daniela
D
Grácio
Health Information and Decision Sciences Department, Faculty of Medicine, University of Oporto, Oporto, Portugal.|CINTESIS - Centre for Health Technology and Services Research, Oporto, Portugal.
Cláudia
C
Dias
Gastroenterology Department, Faculty of Medicine, Centro Hospitalar São João, Oporto, Portugal.
Marco
M
Silva
Gastroenterology Department, Faculty of Medicine, Centro Hospitalar São João, Oporto, Portugal.
Armando
A
Peixoto
Department of Internal Medicine, Faculty of Medicine, University of Porto and Centro Hospitalar São João, Porto, Portugal.
Pedro
P
Lopes
National Institute of Health - Environmental Health Department, Oporto, Portugal.|EPIUnit - Institute of Public Health, University of Oporto, Oporto, Portugal.
Carla
C
Costa
National Institute of Health - Environmental Health Department, Oporto, Portugal.|EPIUnit - Institute of Public Health, University of Oporto, Oporto, Portugal.
João Paulo
JP
Teixeira
Gastroenterology Department, Faculty of Medicine, Centro Hospitalar São João, Oporto, Portugal.
Guilherme
G
Macedo
MedInUP - Centre for Drug Discovery and Innovative Medicines, University of Oporto, Oporto, Portugal fm@med.up.pt.|Gastroenterology Department, Faculty of Medicine, Centro Hospitalar São João, Oporto, Portugal.|Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Oporto, Portugal.
Fernando
F
Magro
D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications / Q000473:pathology; D020552:Comet Assay; D003424:Crohn Disease / Q000150:complications / Q000473:pathology; D004249:DNA Damage; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011446:Prospective Studies
DNA damage; Inflammatory bowel disease; risk factors