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
- 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 2 Department of Otolaryngology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- 3 International Master/PhD Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 4 Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- 5 Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- 6 Department of Surgery, School of Medicine, College of Surgery, Taipei Medical University, Taipei, Taiwan
- 7 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
- 8 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
- 9 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- 10 Department of Medical Research, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan
- 11 Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA
- 12 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- 13 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
- 14 Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- 15 Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- 16 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan
Received: February 16, 2022 Accepted: May 10, 2022 Published: May 19, 2022
https://doi.org/10.18632/aging.204089How to Cite
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.
Abbreviations
AOR: adjusted odds ratio; CI: confidence intervals; GEO: Gene Expression Omnibus; GEPIA: Gene Expression Profiling Interactive Analysis; GTEx: Genotype-Tissue Expression; HNSCC: head and neck squamous cell carcinoma; HRH1: histamine receptor H1; HWE: Hardy-Weinberg equilibrium; OSCC: oral squamous cell carcinoma; SNP: single-nucleotide polymorphism; TCGA: The Cancer Genome Atlas; TNM: tumor, node, metastasis.