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Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer

The Pharmacogenomics Journal volume 17, pages 528–534 (2017)Cite this article

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Abstract

Immunomodulator-targeting therapies are under development in gastric cancer (GC). However, the role of genes modulating anti-tumor immunity in GC remains poorly understood. We investigated the association of variations in genes involved in immunomodulatory pathways with overall survival (OS) in locoregional GC patients. Extracted genomic DNA was analyzed for 35 functional single-nucleotide polymorphisms in genes, PDCD1, CD274, CTLA4, FOXP3, LAG3, ADORA2A, NT5E and IDO1, in 162 Japanese patients as discovery set and 277 US patients as validation set. The C allele of PDCD1 rs10204525 had univariate and multivariable associations with shorter OS in Japanese cohort (P=0.015, P=0.043, respectively). In US cohort the C allele predicted worse OS (P=0.007). Univariate and multivariable analyses revealed IDO1 rs9657182 associated with OS in the Japanese cohort; moreover, the association was confirmed in the US cohort. Genetic predisposition of the host in the immunomodulators may serve as a prognostic biomarker in patients with locoregional GC.

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Acknowledgements

We thank the Dhont Family Foundation and San Pedro Peninsula Cancer Guild that partly funded this study. We also thank the Conquer Cancer Foundation of the American Society of Clinical Oncology and the 2014 Scientific Program Committee for assistance with Y Sunakawa to attend the 2014 ASCO Annual Meeting in Chicago, Illinois, for presentation of current study. S Stremitzer is the recipient of an Erwin Schrödinger fellowship from the Austrian Science Fund. MD Berger received a grant from the Swiss Cancer League (BIL KLS-3334-02-2014). S Stintzing was supported by a postdoctoral fellowship from the German Cancer Aid (the Mildred-Scheel Foundation). A Sebio is the recipient of a Rio Hortega Research Grant from the Insituto de Salud Carlos III (CM11/00102). This study was partly funded by the the National Cancer Institute and award number P30CA014089. 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.

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Authors and Affiliations

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

    Y Sunakawa, N B Volz, M D Berger, A Parekh, W Zhang, S Matsusaka, Y Ning, S Stremitzer, S Stintzing, A Sebio, S Okazaki, T Wakatsuki & H-J Lenz

  2. Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan

    Y Sunakawa

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

    S Cao, D Yang & A H Wu

  4. Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    M Azuma & W Koizumi

  5. Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    M Watanabe

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  1. Y Sunakawa
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Correspondence to Y Sunakawa.

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Sunakawa, Y., Cao, S., Volz, N. et al. Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer. Pharmacogenomics J 17, 528–534 (2017). https://doi.org/10.1038/tpj.2016.46

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  • DOI: https://doi.org/10.1038/tpj.2016.46

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