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It is not yet clearly known how pH affects the bile\u2010induced activation of NF\u2010\u03baB and its related oncogenic pathway previously linked to hypopharyngeal carcinogenesis. In this study, repetitive applications of conjugated primary bile acids with unconjugated secondary bile acid, deoxycholic acid (DCA), on human hypopharyngeal primary cells reveal that strongly acidic pH (4.0) optimally enhances the tumorigenic effect of bile, by inducing activation of NF\u2010\u03baB, STAT3 nuclear translocation, bcl\u20102 overexpression and significant overexpression of the oncogenic mRNA phenotype, compared to weakly acidic pH (5.5) or neutral pH (7.0). As the pH becomes less acidic the partially activated primary bile acids and activated DCA begin to exert their influence; however, with significantly less intensity compared to bile acids at strongly acidic pH. Our findings suggest that biliary tumorigenic effect is strongly pH dependent. Controlling pH during reflux events may be therapeutically effective in reducing the potential risk of bile\u2010induced hypopharyngeal cancer.<\/jats:p>","DOI":"10.1002\/cam4.2194","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T09:38:28Z","timestamp":1559900308000},"page":"4417-4427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Biliary tumorigenic effect on hypopharyngeal cells is significantly enhanced by pH reduction"],"prefix":"10.1002","volume":"8","author":[{"given":"Sotirios G.","family":"Doukas","sequence":"first","affiliation":[{"name":"The Yale Larynx Laboratory Department of Surgery Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Cardoso","sequence":"additional","affiliation":[{"name":"The Yale Larynx Laboratory Department of Surgery Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob I.","family":"Tower","sequence":"additional","affiliation":[{"name":"The Yale Larynx Laboratory Department of Surgery Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-5790","authenticated-orcid":false,"given":"Dimitra P.","family":"Vageli","sequence":"additional","affiliation":[{"name":"The Yale Larynx Laboratory Department of Surgery Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarence T.","family":"Sasaki","sequence":"additional","affiliation":[{"name":"The Yale Larynx Laboratory Department of Surgery Yale School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"American Cancer Society.Laryngeal and hypopharyngeal cancer.2019.https:\/\/www.cancer.org\/cancer\/laryngeal-and-hypopharyngeal-cancer\/about\/key-statistics.html. 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