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

The Pharmacogenomics Journal volume 16, pages 312–319 (2016)Cite this article

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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.

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Acknowledgements

The project described was supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. AS is a recipient of a Juan Rodés contract from the Instituto de Salud Carlos III (JR14/00006). SS is a recipient of the Erwin Schrödinger Fellowship Grant from the Austrian Science Fund.

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Authors and Affiliations

  1. Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles,, CA, USA

    A Sebio, S Matsusaka, W Zhang, D Yang, Y Ning, S Stremitzer, S Stintzing, Y Sunakawa, S Yamauchi & H-J Lenz

  2. Medical Oncology Department, Santa Creu i Sant Pau Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain

    A Sebio

  3. Department of Hematology and Oncology, Klinikum der Universitat, University of Munich, Munich, Germany

    S Stintzing

  4. Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

    Y Fujimoto & M Ueno

  5. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles,, CA, USA

    H-J Lenz

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  1. A Sebio
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Correspondence to H-J Lenz.

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Sebio, A., Matsusaka, S., Zhang, W. et al. Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stages II/III colon cancer. Pharmacogenomics J 16, 312–319 (2016). https://doi.org/10.1038/tpj.2015.64

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