Genetic variants in fas signaling pathway genes and risk of gastric cancer

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作者：

Paula L. Hyland，Shih-Wen Lin，Nan Hu，Han Zhang，Lemin Wang，Hua Su，Chaoyu Wang，Ti Ding，Ze-Zhong Tang，Jin-Hu Fan，You-Lin Qiao，Xiaoqin Xiong，William Wheeler，Carol Giffen，Kai Yu，Jeff Yuenger，Laurie Burdett，Zhaoming Wang，Stephen J. Chanock，Margaret A. Tucker，Sanford M. Dawsey，Neal D. Freedman，Alisa M. Goldstein，Christian C. Abnet，Philip R. Taylor

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摘要：

Populations in north central China are at high risk for gastric cancers (GC), and altered FAS-mediated cell signaling and/or apoptosis may contribute to this risk. We examined the association of 554 single nucleotide polymorphisms (SNPs) in 53 Fas signaling-related genes using a pathway-based approach in 1758 GC cases (1126 gastric cardia adenocarcinomas (GCA) and 632 gastric noncardia adenocarcinomas (GNCA)), and 2111 controls from a genome-wide association study (GWAS) of GC in ethnic Chinese. SNP associations with risk of overall GC, GCA and GNCA were evaluated using unconditional logistic regressions controlling for age, sex and study. Gene- and pathway-based associations were tested using the adaptive rank-truncated product (ARTP) method. Statistical significance was evaluated empirically by permutation. Significant pathway-based associations were observed for Fas signaling with risk of overall GC (p = 5.5E-04) and GCA (p = 6.3E-03), but not GNCA (p= 8.1E-02). Among examined genes in the Fas signaling pathway, MAP2K4, FAF1, MAPK8, CASP10, CASP8, CFLAR, MAP2K1, CAP8AP2, PAK2 and IKBKB were associated with risk of GC (nominal p FAF1 and MAPK8 were significantly associated with risk of both GCA and GNCA (nominal p

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关键词：

gastric cancer gastric cardia gastric noncardia Fas signaling genetic variants GWAS single nucleotide polymorphisms pathway genes