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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations


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
Issue number13
StatePublished - 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.


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


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