Germline Alterations in Patients With IBD-associated Colorectal Cancer.
Inflamm Bowel Dis
; 28(3): 447-454, 2022 03 02.
Article
em En
| MEDLINE
| ID: mdl-34347074
ABSTRACT
BACKGROUND:
Patients with inflammatory bowel diseases (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), are at risk of developing a colorectal cancer (CRC). No information is available on the contribution of patients' genetic background to CRC occurrence. This study investigates germline alterations in patients with IBD-associated CRC.METHODS:
We profiled a panel of 39 genes potentially involved in cancer predisposition and searched for germline variants in IBD patients with CRC or high-grade dysplasia.RESULTS:
After clinical exclusion of genetic cancer syndromes, 25 IBD patients (4 CD and 21 UC) with CRC or high-grade dysplasia were studied. After excluding variants with low likelihood of pathogenicity (classes 1 or 2 according the International Agency for Research on Cancer [IARC]), the panel identified pathogenic variants, likely pathogenic, or variants with unknown significance in 18 patients (72%). Six patients (24%) carried pathogenic or likely variants (IARC class 5 or 4). Of the identified variants, 4 encompassed the APC region, 3 the MLH1 gene, and the remaining ones the MSH2, MSH3, monoallelic MUTYH, EPCAM, BRCA1, CHEK2, POLD1, POLE, CDKN2A, and PDGFRA genes. Four patients carried at least 2 variants in different genes. Duration of IBD was significantly shorter in carriers of 4 or 5 IARC variants (7 years; range 0-21; P = .002) and in those with variants with unknown significance (12 years; range 0-22; P = .005) compared with patients without or with only benign variations (23.5 years; range 15-34).CONCLUSIONS:
In silico analysis and sequence-based testing of germline DNA from IBD patients with CRC or high-grade dysplasia detected 24% of variants positioned in pathogenic classes. In patients with type 3, 4, and 5 variants, the onset of high-grade dysplasia or CRC was significantly earlier than in patients with benign or unidentified variants. The screening for these genes could identify IBD patients requiring a more intensive endoscopic surveillance for earlier detection of dysplastic changes.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Doenças Inflamatórias Intestinais
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Colite Ulcerativa
/
Doença de Crohn
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Inflamm Bowel Dis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália