High cumulative risk of colorectal cancers and desmoid tumours and fibromatosis in South Asian APC mutation carriers.
J Med Genet
; 59(5): 492-495, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-33766935
ABSTRACT
Management of familial adenomatous polyposis (FAP) is guided by the cumulative risk of colorectal cancer (CRC) and aggressive fibromatosis/desmoid (AF/D). The first non-Caucasian FAP cohort with cumulative risk estimates for CRC and AF/D shows distinct differences with the Caucasian and other Asian cohorts. The strong correlation between the adenomatous polyposis coli (APC) mutation location with the FAP phenotype and the geoethnic differences in APC mutation spectrum, genetic constitution, lifestyle and sporadic CRC rates, mandates the use of population-specific cumulative risk estimates for CRC and desmoid for counselling and risk management. On genotype-phenotype correlation in 83 individuals with classical FAP and a confirmed pathogenic/likely Pathogenic (P/LP) APC variant (n=76) or obligate carrier of the family variant (n=7), we observed a high cumulative CRC risk of 40% and 85% by 40 and 60 years, respectively. The observed 30% cumulative risk by 50 years for desmoids was higher than previous European and Asian cohorts and was significantly associated with prophylactic surgery (OR 4.58, 95% CI 1.06 to 19.78) and APC mutation 3' of codon 1309 (OR 13.07, 95% CI 3.58 to 47.56) and also 3' of codon 1444 (OR 8.0, 95% CI 1.83 to 34.94). Global cooperation is required to establish FAP genotype-phenotype associations and population-specific risk estimates to guide genetic counselling and risk management.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibromatose Agressiva
/
Polipose Adenomatosa do Colo
/
Proteína da Polipose Adenomatosa do Colo
/
Fibroma
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article