Associations of long non-coding RNAs HOTAIR, LINC00951, POLR2E and HULC polymorphisms with the risk of esophageal and esophagogastric junction cancer in a western population: a case-control study

Abstract

Background: The incidence of single-nucleotide-polymorphisms with malignant potential in esophageal cancer tissues has only been sparsely investigated in the west. Hence, we explored the contribution of four long non-coding RNAs' polymorphisms HOTAIR rs920778, LINC00951 rs11752942, POLR2E rs3787016 and HULC rs7763881 in esophageal cancer susceptibility.

Methods and results: Formalin-fixed paraffin-embedded tissue specimens from 95 consecutive patients operated for esophageal/esophagogastric junction carcinoma during 25/03/2014-25/09/2018 were processed. Demographic data, histopathological parameters, surgical and oncological outcomes were collected. DNA findings of the abovementioned population were compared with 121 healthy community controls. Both populations were of European/Greek ancestry. Sixty-seven patients underwent Ivor Lewis/McKeown esophagectomy for either squamous cell esophageal carcinoma (N = 6) or esophageal/esophagogastric junction Siewert I or II adenocarcinoma (N = 61). Twenty-eight patients were subjected to extended total gastrectomy for esophagogastric junction Siewert III adenocarcinoma. Neither LINC00951 rs11752942 nor HULC rs7763881 polymorphisms were detected more frequently in esophageal cancer patients compared with healthy community subjects. A significantly higher presence of HOTAIR rs920778 TT genotype in esophagogastric junction Siewert I/II adenocarcinoma was identified. POLR2E rs3787016 C allele and CC genotypes were overrepresented in the control group, and when found in esophageal cancer carriers were associated with earlier disease stages, as well as with minor lymph node involvement and lesser metastatic potential.

Conclusions: HOTAIR rs920778 may serve as a potential therapeutic suppression target, while POLR2E rs3787016 may represent a valuable biomarker to evaluate esophageal cancer predisposition and predict treatment response and prognosis. Clinical implications of these findings need to be verified with further prospective studies with larger sample-size.

Keywords: Esophageal cancer; Esophagogastric junction carcinoma; HOTAIR rs920778; LINC00951 rs11752942; Long noncoding RNAs (lncRNAs); POLR2E rs3787016 and HULC rs7763881; Single-nucleotide-polymorphisms (SNPs).