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

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

Genetic Susceptibility in Head and Neck Squamous Cell Carcinoma in a Spanish Population

Despite classical environmental risk factors like tobacco, alcohol or viral infection, not all individuals develop head and neck cancer. Therefore, identification of the genetic susceptibility produced by single nucleotide polymorphisms (SNPs) is an important task. A total of 296 human papillomavirus negative head and neck cancer (HNC) patients (126 laryngeal, 100 pharyngeal and 70 oral cavity) were included in the study, involving 29 candidate SNPs in genes within important carcinogenic pathways (oncogenesis and tumour suppression, DNA repair, inflammation, oxidation and apoptosis). Genotyping was performed using TaqMan probes or restriction fragment length assays in peripheral blood DNA. In addition, 259 paired controls were also evaluated with the same risk factors for each specific location. Nine SNPs in DNA repair (ERCC1 rs11615, ERCC2 rs13181), inflammatory (IL2 rs2069762, IL6 rs1800795), oxidative (NFE2L2 rs13035806 and rs2706110) and apoptotic genes (TP53 rs1042522, MDM2 rs2279744, BCL2 rs2279115) were differently associated with HNSCC susceptibility by location. Some of these SNPs were not described before in this tumour type. In conclusion, we describe several SNPs associated with HNC in a Spanish population

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p<0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p<0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours

Caracterización de variantes genéticas implicadas en la susceptibilidad a desarrollar carcinomas escamosos de cabeza y cuello. Correlación clínica

[EN] Crowd of exogenous agents (snuff , alcohol ,ultraviolet radiation, etc.) And endogenous agents (hydrogen peroxide, reactive oxygen molecules , etc.) can cause DNA damage. Polymorphisms in DNA repair genes may alter the ability to repair DNA damage, lead to genetic instability and carcinogenesis. Furthermore, considering that cancer treatments are often based on the induction of DNA damage , polymorphisms in repair pathways could be important for treatment response , toxicity and survival. Moreover, numerous studies show that the allelic variant of codon 72 of P53 has different functional activity in the induction of apoptosis , an essential mechanism behind the failure of repair systems . In this context we consider the following objectives: 1 - . Study , in patients diagnosed with head and neck cancer, the presence of allelic variants in DNA repair genes ( XRCC1_rs25487 , APEX_rs1130409 , XPD_rs13181 , ERCC1_rs11615 , XRCC3_rs861539 ) and p53 codon 72 ( rs1042522 ) , which may alter the risk of developing the disease. 2 - . To analyze the possible involvement of these allelic variants in disease-free survival , response to treatment and the occurrence of side effects in patients with head and neck tumors.[ES] Multitud de agentes tanto exógenos (tabaco, alcohol, radiaciones ultravioleta, etc.) como endógenos (agua oxigenada, moléculas de oxígeno reactivas,etc.) pueden producir daño en el ADN. Polimorfismos en los genes reparadores del ADN podrían alterar la capacidad de reparación del daño al ADN, conducir a inestabilidad genética y carcinogénesis. Además, teniendo en cuenta que los tratamientos del cáncer se basan a menudo en la inducción del daño al ADN, polimorfismos en las vías de reparación podrían ser importantes para la respuesta al tratamiento, toxicidad y supervivencia. Por otra parte, numerosos estudios demuestran que la variante alélica del codón 72 de P53 posee diferente actividad funcional en la inducción de la apoptosis, mecanismo imprescindible tras el fallo de los sistemas de reparación. En este contexto nos planteamos los siguientes objetivos: 1-. Estudiar, en pacientes diagnosticados de cáncer de cabeza y cuello, la presencia de variantes alélicas en genes reparadores del ADN (XRCC1_rs25487, APEX_rs1130409, XPD_rs13181, ERCC1_rs11615, XRCC3_rs861539) y en el codón 72 de p53 (rs1042522), que puedan modificar el riesgo de desarrollar la enfermedad. 2-. Analizar la posible implicación de dichas variantes alélicas en la supervivencia libre de enfermedad, respuesta al tratamiento y en la aparición de efectos secundarios en los pacientes con tumores de cabeza y cuello