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Cited by 24Esophageal Cancer Research and TreatmentGenetic Associations and EpidemiologyGastric Cancer Management and Outcomes

Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a Chinese Population

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Li, Wen-Qing, Hu, Nan, Wang, Zhaoming, Yu, Kai, Su, Hua, Wang, Lemin, Wang, Chaoyu, Chanock, Stephen J. +15 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0068999PMC PMC3715462
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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.

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  • Population studies and microarray analyses revealed PLCγ2 associated with the EGFR pathway was a risk factor in esophageal squamous cell carcinoma and gastric cancer.

    “Population studies and microarray analyses also revealed PLCγ2 associated with the EGFR pathway was a risk factor in esophageal squamous cell carcinoma and gastric cancer (149), in non–small-cell lung cancer associated with HMGB1 expression (150), and as upregulated and potentially involved in triple-negative breast cancer–associated BRAC1 in a Chinese patient cohort (151).”

    From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [149]

    The Abstract (page not available) lists PLCG2 among EGFR-pathway genes associated with gastric cancer risk, but lists different genes for esophageal squamous cell carcinoma. The Methods describe an analysis of genetic variants using GWAS data, not a microarray expression analysis. The paper treats these as associations requiring validation, rather than establishing PLCγ2 as a risk factor for both cancers. (LLM, conf=0.90)

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Cited by

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Authors
Li, W.-Q., Hu, N., Wang, Z., Yu, K., Su, H., Wang, L., Wang, C., Chanock, S. J., Burdett, L., Ding, T., Qiao, Y.-L., Fan, J.-H., Wang, Y., Xu, Y., Giffen, C., Xiong, X., Murphy, G., Tucker, M. A., Dawsey, S. M., Freedman, N. D., Abnet, C. C., Goldstein, A. M., & Taylor, P. R.
Affiliations
  • National Institutes of Health (US)
  • National Cancer Institute (US)
  • Shanxi Provincial Cancer Hospital (CN)
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • Information Management Services (US)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-07-18
Volume
8
Issue
7
Pages
e68999
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0068999
PMC
PMC3715462
OpenAlex
W2058904803
Cited by
24
References
0
Citations by year
2026: 2 · 2024: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 4 · 2014: 5 · 2013: 1
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Chinese Academy of Medical Sciences
  • National Institutes of Health (n01sc091030-001)
  • National Cancer Institute (N02-SC-66211, N01 SC 91030, HHSN261200477001C)
Topics
  • Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
Keywords
esophageal squamous cell carcinoma, gastric cancer, germline genetic variants, single nucleotide polymorphisms, cancer susceptibility, Han Chinese, Fyn, JNK1, MAP2K4, GNAI3, MEK1, talin-1, prolactin receptor, PLCγ2, PIK3R3, CHRNE, PAK4, WASL, pruritus
MeSH terms
Esophageal Squamous Cell Carcinoma, Carcinoma, Squamous Cell, China, Esophageal Neoplasms, Genotype, Humans, Stomach Neoplasms, Genetic Variation, Signal Transduction, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People, Genetic Association Studies, ErbB Receptors

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