title: Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population.
abstract: The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10(-3)). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. liw9@mail.nih.gov
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.forename: Lemin
authors.initials: L
authors.lastname: Wang
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdett
authors.forename: Ti
authors.initials: T
authors.lastname: Ding
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: Jin-Hu
authors.initials: JH
authors.lastname: Fan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xiong
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tucker
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
mesh_terms: D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D002681:China / Q000453:epidemiology; D066246:ErbB Receptors / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D066246:ErbB Receptors