Open AccessGenetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer
Author(s) -
Yu Sunakawa,
Shu Cao,
Nico Volz,
Martin D. Berger,
Dongyun Yang,
Anish Parekh,
W Zhang,
Satoshi Matsusaka,
Yan Ning,
Stefan Stremitzer,
Sebastian Stintzing,
Ana Sebio,
Satoshi Okazaki,
Takeru Wakatsuki,
Mizutomo Azuma,
Masahiko Watanabe,
Wasaburo Koizumi,
Anna H. Wu,
Lenz Hj
Publication year - 2016
Publication title -
pharmacogenomics journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.804
H-Index - 85
eISSN - 1473-1150
pISSN - 1470-269X
DOI - 10.1038/tpj.2016.46
Subject(s) - cohort , cancer , oncology , medicine , single nucleotide polymorphism , allele , genotype , univariate analysis , gene , biomarker , biology , genetics , multivariate analysis
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.