Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stage II/III colon cancer
Sebio, Ana (Institut d'Investigació Biomèdica Sant Pau)
Matsusaka, Satoshi (Keck School of Medicine, University of Southern California)
Zhang, Wu (Keck School of Medicine, University of Southern California)
Yang, Dongyun (Keck School of Medicine, University of Southern California)
Ning, Yan (Keck School of Medicine, University of Southern California)
Stremitzer, Stefan (Keck School of Medicine, University of Southern California)
Stintzing, Sebastian (Department of Hematology and Oncology, Klinikum der Universitat, University of Munich, Munich, Germany)
Sunakawa, Yu (Keck School of Medicine, University of Southern California)
Yamauchi, Shinichi (Keck School of Medicine, University of Southern California)
Fujimoto, Yoshiya (Cancer Institute Hospital. Department of Gastroenterological Surgery (Tokyo))
Ueno, Masashi (Cancer Institute Hospital. Department of Gastroenterological Surgery (Tokyo))
Lenz, Heinz-Josef (Keck School of Medicine, University of Southern California)
Universitat Autònoma de Barcelona

Date:	2015
Abstract:	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.
Grants:	Instituto de Salud Carlos III JR14/00006
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Polymorphisms ; Hippo pathway ; Colon cancer ; Recurrence ; Biomarkers
Published in:	The pharmacogenomics journal, Vol. 16 (september 2015) , p. 312-319, ISSN 1473-1150

DOI: 10.1038/tpj.2015.64
PMID: 26370619

22 p, 644.2 KB

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