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

Sunakawa, Y; Cao, S; Volz, N B; Berger, Martin Dave; Yang, D; Parekh, A; Zhang-Wu, Xiaxia; Matsusaka, S; Ning, Y; Stremitzer, S; Stintzing, S; Sebio, A; Okazaki, S; Wakatsuki, T; Azuma, M; Watanabe, M; Koizumi, W; Wu, A H; Lenz, H-J (2017). Genetic variations in immunomodulatory pathways to predict survival in patients with locoregional gastric cancer. Pharmacogenomics journal, 17(6), pp. 528-534. Nature Publishing Group 10.1038/tpj.2016.46

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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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