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We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk\u00a0of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome\u2010wide association study datasets. In the single\u2010locus analysis, we identified two SNPs (rs145533669 and rs35246205) in\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    to be associated with risk of SCCHN (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a01.57\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    and .004, respectively), two SNPs (\n                    <jats:italic>EPHX1<\/jats:italic>\n                    rs117522494 and\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    rs145533669) to be associated with risk of oropharyngeal cancer (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.001 and .004, respectively), and one SNP (rs4359199 in\n                    <jats:italic>HSD17B12<\/jats:italic>\n                    ) to be associated with risk of oral cancer (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a0.006). A significant interaction effect was found between rs4359199 and drinking status on risks of SCCHN and oropharyngeal cancer (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.05). eQTL and sQTL analyzes revealed that two SNPs (\n                    <jats:italic>CYP2B6<\/jats:italic>\n                    rs35246205 and\n                    <jats:italic>HSD17B12<\/jats:italic>\n                    rs4359199) were correlated with alternative splicing or mRNA expression levels of the corresponding genes in liver cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.05 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\u2010wide association studies presented significant associations between these genes and risks of other cancers, smoking behavior and alcohol dependence (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009.05). Thus, our study provided some insight into the underlying genetic mechanism of head and neck cancer, which warrants future functional validation.\n                  <\/jats:p>","DOI":"10.1002\/ijc.34023","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T09:45:29Z","timestamp":1649670329000},"page":"553-564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genetic variants in\n                    <i>CYP2B6<\/i>\n                    and\n                    <i>HSD17B12<\/i>\n                    associated with risk of squamous cell carcinoma of the head and neck"],"prefix":"10.1002","volume":"151","author":[{"given":"Hongliang","family":"Liu","sequence":"first","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Population Health Sciences Duke University Medical School  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-1502","authenticated-orcid":false,"given":"Guojun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-4822","authenticated-orcid":false,"given":"Erich M.","family":"Sturgis","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Shete","sequence":"additional","affiliation":[{"name":"Department of Epidemiology The University of Texas MD Anderson Cancer Center  Houston Texas USA"},{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8116-9558","authenticated-orcid":false,"given":"Kristina R.","family":"Dahlstrom","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Biostatistics, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher I.","family":"Amos","sequence":"additional","affiliation":[{"name":"The Institute for Clinical and Translational Research Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"},{"name":"Department of Medicine Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-9445","authenticated-orcid":false,"given":"Qingyi","family":"Wei","sequence":"additional","affiliation":[{"name":"Duke Cancer Institute Duke University Medical Center  Durham North Carolina USA"},{"name":"Department of Population Health Sciences Duke University Medical School  Durham North Carolina 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