Lynch syndrome: influence of additional susceptibility variants on cancer risk.
Eur J Hum Genet
; 31(9): 1078-1082, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37088804
ABSTRACT
Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines. We made the hypothesis that additional germline variants in cancer susceptibility genes (CSG) could explain some of these phenotypes. We compared the prevalence of additional CSG variants in LS patients with a cancer diagnosis before age 30 (early-onset, EO group) and after 40 (usual-onset, UO group). While there was no overall difference, we did find an excess of pathogenic variants and variants of unknown significance in EO cases when only gastrointestinal CSG were considered (OR 2.25; 95% CI 1.01-5.06, p value = 0.04). Four EO cases stood out two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion. Additional germline variants should be considered in future screening recommendations, as they might influence cancer risk.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
/
Hereditariedade
/
Tipos_de_cancer
/
Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais Hereditárias sem Polipose
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Guideline
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
França