J Cancer 2019; 10(13):2907-2914. doi:10.7150/jca.31125

Research Paper

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

Yi-Liang Wu1,2,3,#, Ming-Hsien Chien4,5,#, Ying-Erh Chou2,6, Jer-Hwa Chang5,7,8, Tu-Chen Liu1,9, Thomas Chang-Yao Tsao2,10, Ming-Chih Chou1,3, Shun-Fa Yang1,6,✉

1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan
3. Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
4. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5. Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
6. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
7. Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
8. Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
9. Department of Chest Medicine, Cheng-Ching General Hospital, Taichung, Taiwan
10. Division of Chest, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
#These authors contributed equally to this work.

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Citation:
Wu YL, Chien MH, Chou YE, Chang JH, Liu TC, Tsao TCY, Chou MC, Yang SF. Association of EGFR mutations and HMGB1 genetic polymorphisms in lung adenocarcinoma patients. J Cancer 2019; 10(13):2907-2914. doi:10.7150/jca.31125. Available from http://www.jcancer.org/v10p2907.htm

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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.

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