Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stage II/III colon cancer

The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil. In this study 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were eval...

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Detalles Bibliográficos
Autores: Sebio, Ana|||0000-0003-3333-2370, Matsusaka, Satoshi, Zhang, Wu, Yang, Dongyun, Ning, Yan, Stremitzer, Stefan, Stintzing, Sebastian, Sunakawa, Yu, Yamauchi, Shinichi, Fujimoto, Yoshiya, Ueno, Masaki, Lenz, Heinz-Josef
Tipo de recurso: artículo
Fecha de publicación:2015
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:185417
Acceso en línea:https://ddd.uab.cat/record/185417
https://dx.doi.org/urn:doi:10.1038/tpj.2015.64
Access Level:acceso abierto
Palabra clave:Polymorphisms
Hippo pathway
Colon cancer
Recurrence
Biomarkers
Descripción
Sumario:The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil. In this study 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56% vs 33%, HR: 1.87; p =0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28% vs 40%; HR: 0.66; p =0.07). In left-sided tumors, this association was stronger (HR: 0.29; p =0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stage II and III colon cancer.