Sasaki CT, et al. - In this pilot study, researchers analyzed NF-κB–related messenger RNA (mRNA) and microRNA oncogenic phenotypes in bile-related human hypopharyngeal squamous cell carcinoma (HSCC), similar to those earlier recognized in acidic bile–exposed premalignant murine hypopharyngeal mucosa. An intense NF-κB activation along with significant overexpression of RELA(p65), EGFR, STAT3, BCL-2, cREL, ΔNp63, WNT5A, IL-6, and IL1B; upregulation of oncomir miR-21; and downregulation of tumor suppressor miR-375 was shown by bile(+) HSCC vs their respective adjacent normal tissues (ANTs). Significantly higher mRNA levels were shown by bile(+) HSCC of all the analyzed genes, especially RELA(p65), IL-6, EGFR, and TNF-α than bile(-) tumors. In bile(+) HSCCs vs their ANTs and bile(-) tumors, >260-fold and >30-fold higher miR-21/miR-375 ratio, which earlier has been associated with tumor aggressiveness, was found, respectively. According to novel findings, a history of bile as a part of esophageal reflux disease could independently confer risk for hypopharyngeal carcinogenesis.