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Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma. ATG5 rs2245214 SNP was not associated with any location. Overall, our results indicate the importance of the autophagy pathway in the susceptibility of head and neck squamous cell carcinoma and demonstrate the heterogeneity between its locations encompassed under a single terminology.

SUBMITTER: Fernandez-Mateos J

PROVIDER: S-EPMC5537226 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma.

Fernández-Mateos Javier J Seijas-Tamayo Raquel R Klain Juan Carlos Adansa JCA Borgoñón Miguel Pastor MP Pérez-Ruiz Elisabeth E Mesía Ricard R Del Barco Elvira E Coloma Carmen Salvador CS Dominguez Antonio Rueda AR Daroqui Javier Caballero JC Fernández Ruiz Encarnación E Cruz-Hernández Juan Jesús JJ González-Sarmiento Rogelio R

Scientific reports 20170731 1

Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16 ...[more]

PMID: 28761177

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Project description:Patients who have undergone curative?intent therapy for head and neck squamous cell carcinoma (HNSCC) exhibit a high rate of development of second primary tumors (SPTs), which are frequently lethal. A chemoprevention strategy that prevents SPTs would have a major impact on patient outcomes. Sulforaphane, a naturally?occurring compound derived from cruciferous vegetables exhibits chemopreventive activity against HNSCC in a preclinical model. The effects of sulforaphane are considered to be mediated, in large part, through increased protein expression of the transcription factor nuclear factor erythroid 2?related factor 2 (NRF2). Development of sulforaphane chemoprevention for HNSCC would benefit from the identification of robust biomarkers of sulforaphane activity in HNSCC cells and normal mucosal epithelial cells. The present study revealed that sulforaphane potently induces multiple oxidative stress?associated genes at the RNA and protein levels, in HNSCC cells and Het?1A cells, a non?tumorigenic mucosal epithelial cell line. In the present analysis, HMOX1 and HSPA1A were identified as the most highly upregulated genes following sulforaphane treatment, suggesting their potential value as biomarkers to guide clinical trials. Sulforaphane induction of HMOX1 and HSPA1A was validated in vivo in murine tissues. Furthermore, the impact of sulforaphane treatment of HNSCC cells on the expression levels of natural killer group 2D (NKG2D) and DNAX accessory molecule?1 (DNAM?1) ligands, which are activators of natural killer (NK) cells, was examined. NRF2?dependent upregulation of the NKG2D ligand MICA/B was observed. However, only one of the six HNSCC cell lines studied exhibited enhanced sensitivity to NK cell?mediated killing following sulforaphane treatment, suggesting that this may not be a general mechanism of sulforaphane chemopreventive activity in HNSCC. In summary, the present study identified robust biomarkers of sulforaphane activity in HNSCC and normal tissues, supporting their application in the development of sulforaphane chemoprevention approaches for HNSCC.

Dataset Information

Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma.

Publications

Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma.

Similar Datasets

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