title: Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer.
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.
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Division of Medical Oncology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Yokohama, Kanagawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sunakawa
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cao
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Volz
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Berger
authors.affiliation: Department of Preventive Medicine, 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: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Parekh
authors.affiliation: 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: 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: 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: 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: 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: Stintzing
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sebio
authors.affiliation: 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: Okazaki
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wakatsuki
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Koizumi
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Division of Medical Oncology, 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: D000230:Adenocarcinoma / Q000276:immunology* / Q000401:mortality* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D013274:Stomach Neoplasms / Q000276:immunology* / Q000401:mortality* / Q000628:therapy
chemical_list: C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor