TY - JOUR
T1 - Genetic variants in CYP2B6 and HSD17B12 associated with risk of squamous cell carcinoma of the head and neck
AU - Liu, Hongliang
AU - Li, Guojun
AU - Sturgis, Erich M.
AU - Shete, Sanjay
AU - Dahlstrom, Kristina R.
AU - Du, Mulong
AU - Amos, Christopher I.
AU - Christiani, David C.
AU - Lazarus, Philip
AU - Wei, Qingyi
N1 - Publisher Copyright:
© 2022 UICC.
PY - 2022/8/15
Y1 - 2022/8/15
N2 - 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.
AB - 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.
KW - GWAS
KW - molecular epidemiology
KW - PAH metabolism
KW - SNP
KW - squamous cell carcinoma of the head and neck
KW - tobacco-specific nitrosamines
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U2 - 10.1002/ijc.34023
DO - 10.1002/ijc.34023
M3 - Article
C2 - 35404482
AN - SCOPUS:85129939593
SN - 0020-7136
VL - 151
SP - 553
EP - 564
JO - International journal of cancer
JF - International journal of cancer
IS - 4
ER -