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Research Paper|Volume 14, Issue 10|pp 4500—4512

Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma

Yi-Fang Ding1,2, Yung-Wei Lin3,4, Wen-Kuan Chiu5,6, Chiao-Wen Lin7,8, Yi-Chieh Yang9,10, Lun-Ching Chang11, Jungshan Chang1, Shun-Fa Yang12,13, Ming-Hsien Chien9,14,15,16
  • 1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 2Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  • 3International Master/PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 4Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  • 5Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  • 6Department of Surgery, School of Medicine, College of Surgery, Taipei Medical University, Taipei, Taiwan
  • 7Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
  • 8Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 9Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • 10Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
  • 11Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA
  • 12Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 13Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 14Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
  • 15Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
  • 16TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan
Received: February 16, 2022Accepted: May 10, 2022Published: May 19, 2022
https://doi.org/10.18632/aging.204089

Copyright: © 2022 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.