[Genetic alterations, genomic instability and cancer in celiac disease].
Celiac disease (CD) is a common autoimmune disorder characterized by intestinal inflammation and mucosal atrophy triggered by dietary gluten in genetically predisposed individuals. Although, most patients improve with a gluten-free diet, a small percentage (2-5%) develops refractoriness or pre- and malignant complications. Malignancies are the most serious complications of CD, including gastrointestinal carcinomas and non-Hodgkin lymphoma, particularly Enteropathy-type T-cell lymphoma, a rare high-grade T-cell non-Hodgkin lymphoma of the small intestine, almost exclusively observed in CD patients. The molecular basis behind cancer development in CD is not known. To really understand CD-cancer biology it is important to known all of its genetic and genomic alterations. Carcinogenesis involves the acquisition of multiple genetic changes that create a background of genetic instability which accelerate the accumulation of subsequent mutations. Two major modes of genome destabilization have been recognized: microsatellite instability and chromosome instability (CIN). A review of genetic abnormalities reported in CD, refractory sprue or CD-associated tumors, suggests that a CIN phenotype is implied in malignant transformation in CD. Moreover, our recent findings showing that a group of untreated CD patients exhibits genomic instability at nucleotide level, affecting specific microsatellite loci, provides evidence of molecular alterations in non-malignant CD cells. In conclusion, most genetic studies, point to the role of chronic inflammation in the induction of genomic instability and malignant emergence in at-risk individuals.
Fundia
Ariela F
AF
Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R Castex, Academia Nacional de Medicina de Buenos Aires, Argentina. affundia@hematologia.anm.edu.ar
Larripa
Irene
I
Slavutsky
Irma
I
D001327:Autoimmune Diseases / Q000150:complications* / Q000235:genetics; D002446:Celiac Disease / Q000150:complications* / Q000178:diet therapy / Q000235:genetics; D055050:Diet, Gluten-Free; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics*