title: Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stages II/III colon cancer.
abstract: The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil (5-Fu). 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%, hazard ratio (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 stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64.
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Medical Oncology Department, Santa Creu i Sant Pau Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sebio
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stremitzer
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Hematology and Oncology, Klinikum der Universitat, University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sunakawa
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Sharon A. Carpenter Laboratory, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000217:Acyltransferases; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002140:California; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D014041:Tokyo; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C411762:RASSF1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D005472:Fluorouracil