Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck. Article

Liu, Hongliang, Li, Guojun, Sturgis, Erich M et al. (2022). Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck. . 151(4), 553-564. 10.1002/ijc.34023

cited authors

  • Liu, Hongliang; Li, Guojun; Sturgis, Erich M; Shete, Sanjay; Dahlstrom, Kristina R; Du, Mulong; Amos, Christopher I; Christiani, David C; Lazarus, Philip; Wei, Qingyi

fiu authors

abstract

  • Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10-4 and .004, respectively), two SNPs (EPHX1 rs117522494 and CYP2B6 rs145533669) to be associated with risk of oropharyngeal cancer (P = .001 and .004, respectively), and one SNP (rs4359199 in HSD17B12) to be associated with risk of oral cancer (P = .006). A significant interaction effect was found between rs4359199 and drinking status on risks of SCCHN and oropharyngeal cancer (P < .05). eQTL and sQTL analyzes revealed that two SNPs (CYP2B6 rs35246205 and HSD17B12 rs4359199) were correlated with alternative splicing or mRNA expression levels of the corresponding genes in liver cells (P < .05 for both). In silico functional annotation suggested that these two SNPs may regulate mRNA expression by affecting the binding of transcription factors. Results from phenome-wide association studies presented significant associations between these genes and risks of other cancers, smoking behavior and alcohol dependence (P < .05). Thus, our study provided some insight into the underlying genetic mechanism of head and neck cancer, which warrants future functional validation.

publication date

  • August 1, 2022

keywords

  • 17-Hydroxysteroid Dehydrogenases
  • Carcinoma, Squamous Cell
  • Case-Control Studies
  • Cytochrome P-450 CYP2B6
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Head and Neck Neoplasms
  • Humans
  • Oropharyngeal Neoplasms
  • Polymorphism, Single Nucleotide
  • RNA, Messenger
  • Risk Factors
  • Squamous Cell Carcinoma of Head and Neck

Digital Object Identifier (DOI)

Medium

  • Print-Electronic

start page

  • 553

end page

  • 564

volume

  • 151

issue

  • 4