Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients

Yi Liang Wu, Ming Hsien Chien, Ying Erh Chou, Jer Hwa Chang, Tu Chen Liu, Thomas Chang Yao Tsao, Ming Chih Chou, Shun Fa Yang

Research output: Contribution to journalArticle

Abstract

High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of HMGB1 were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR, compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant EGFR, HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p=0.019), compared to patients with TT homozygotes. Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. HMGB1 variants and tobacco consumption might contribute to the pathological development of NSCLC.

Original languageEnglish
Pages (from-to)2907-2914
Number of pages8
JournalJournal of Cancer
Volume10
Issue number13
DOIs
Publication statusPublished - Jan 1 2019

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HMGB1 Protein
Genetic Polymorphisms
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Homozygote
Tobacco Use
Adenocarcinoma of lung
Heterozygote
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Exons
Neoplasms
Alleles
Odds Ratio
Genotype
Confidence Intervals

Keywords

  • Epidermal growth factor receptor
  • High-mobility group protein box 1
  • Non-small-cell lung cancer
  • Polymorphism
  • Susceptibility

ASJC Scopus subject areas

  • Oncology

Cite this

Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients. / Wu, Yi Liang; Chien, Ming Hsien; Chou, Ying Erh; Chang, Jer Hwa; Liu, Tu Chen; Tsao, Thomas Chang Yao; Chou, Ming Chih; Yang, Shun Fa.

In: Journal of Cancer, Vol. 10, No. 13, 01.01.2019, p. 2907-2914.

Research output: Contribution to journalArticle

Wu, Yi Liang ; Chien, Ming Hsien ; Chou, Ying Erh ; Chang, Jer Hwa ; Liu, Tu Chen ; Tsao, Thomas Chang Yao ; Chou, Ming Chih ; Yang, Shun Fa. / Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients. In: Journal of Cancer. 2019 ; Vol. 10, No. 13. pp. 2907-2914.
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