Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain.

BACKGROUND: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1-2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. OBJECTIVE: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1-2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. MATERIALS AND METHOD: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null -), GSTT1 (present + or null -). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent - TC/TT), and CYP1A1-2 A>G (present + GG, or absent - AG/AA). RESULTS: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). CONCLUSIONS: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.

Genotyping of the C>T allele of rs16906252, predictor of O16-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, in erosive atrophic lesions of oral lichen planus.

BACKGROUND: DNA promoter methylation is usually an early stage in carcinogenesis process, including oral cancer. The purpose of this study was to investigate the association between T allele of specific single nucleotide polymorphism (SNP) C>T rs 16906252 and O16-methylguanine-DNA methyltransferase (MGMT) methylation as prospective biomarkers of malignant transformation in oral lichen planus (OLP), a chronic autoimmune mucocutaneous disease. METHODS: This research is an observational, analytical case-control study where a total of 85 subjects (43 control individuals and 42 OLP patients) participated. The samples (mouthwashes) from all volunteers were analyzed, and DNA extraction was carried out. The genotyping of the rs 16906252 SNP in the MGMT gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses of Student t test and multiple logistic regressions were used. RESULTS: C>T genotype in the control and OLP groups was detected in 2.3% and 19.0%, respectively. The presence of this genotype was associated with methylation of the MGMT gene. In fact, taking into account age and gender, subjects with C>T genotype were 10.5 (95% CI 1.03-106; P = 0.047) times more likely to methylate promoter region of the MGMT gene. CONCLUSIONS: These findings indicate that C>T allele of rs 16906252, predictor of MGMT promoter methylation status, may be an important feature in the clinical prognosis of premalignant lesions of OLP, although this finding requires further clinical and laboratory investigation.

The assessment of the Newborn Hearing Screening Program in the Region of Murcia from 2004 to 2012.

OBJECTIVES: Newborn (NB) auditory deficit has a prevalence of 1-2% in the world. Since the 1990s different screening programs have been put into practice. The Newborn Hearing Screening Program has been in operation since 2002 in our hospital (HCUVA) in Murcia (Spain) and two years later it was introduced into the whole of the Autonomous Community of the Region of Murcia as part of universal healthcare. The objective of this study was to analyze and assess its results. METHOD: The newborn (NB) population is divided into two groups: not-at-risk NBs and at-risk NBs. In the first case we carry out acoustic otoemissions (AOEs) 48 h after birth and depending on the result the child is either discharged or, in negative cases, the infant undergoes a series of tests in a period of 30-45 days to confirm or rule out the existence of hearing anomalies. In the at-risk group we combine AOEs with brain trunk potentials (BERA) following the stages in a decision tree diagram similar to the ones for not-at-risk children in order to provide a clinical diagnosis in the first three months of life. RESULTS: The screening performance was assessed for the 156,122 children studied, of which 151,258 belonged to the group of not-at-risk children; and 4864 to the group at risk of hypoacusia. As a result of the screening only 410 (0.26%) were sent to consultation, 213 in the not-at-risk group (0.14%) and 197 (24.7%) in the at-risk group. A total of 7452 false positives were identified (4.7%), 6951 (4.5%) in the not-at-risk group; and 501 (10.3%) in the group with risk factors; and there were 53 false negatives (0.03%). Sensitivity in the screening program was 88.5%, with a specificity of 95%. CONCLUSIONS: The Region of Murcia has a Newborn Hearing Screening Program with tests that provide a high level of sensitivity and specificity in accordance with the findings of the literature. Our results endorse the program and the patients were treated in a way that met the objective of providing a correct diagnosis and the appropriate therapeutic action.

Unbalanced acetylcholinesterase activity in larynx squamous cell carcinoma.

Previous reports have demonstrated that a non-neuronal cholinergic system is expressed aberrantly in airways. A proliferative effect is exerted directly by cholinergic agonists through the activation of nicotinic and muscarinic receptors. In cancer, particularly those related with smoking, the mechanism through which tumour cells respond to aberrantly activated cholinergic signalling is a key question. Fifty paired pieces of larynx squamous cell carcinoma and adjacent non-cancerous tissue were compared in terms of their acetylcholinesterase activity (AChE). The AChE activity in non-cancerous tissues (0.248 ± 0.030 milliunits per milligram of wet tissue; mU/mg) demonstrates that upper respiratory tissues express sufficient AChE activity for controlling the level of acetylcholine (ACh). In larynx carcinomas, the AChE activity decreased to 0.157 ± 0.024 mU/mg (p=0.009). Larynx cancer patients exhibiting low ACh-degrading enzymatic activity had a significantly shorter overall survival (p=0.031). Differences in the mRNA levels of alternatively spliced AChE isoforms and molecular compositions were noted between glottic and supraglottic cancers. Our results suggest that the low AChE activity observed in larynx squamous cell carcinoma may be useful for predicting the outcome of patients.

Dysregulated cholinergic network as a novel biomarker of poor prognostic in patients with head and neck squamous cell carcinoma.

BACKGROUND: In airways, a proliferative effect is played directly by cholinergic agonists through nicotinic and muscarinic receptors activation. How tumors respond to aberrantly activated cholinergic signalling is a key question in smoking-related cancer. This research was addressed to explore a possible link of cholinergic signalling changes with cancer biology. METHODS: Fifty-seven paired pieces of head and neck squamous cell carcinoma (HNSCC) and adjacent non-cancerous tissue (ANCT) were compared for their mRNA levels for ACh-related proteins and ACh-hydrolyzing activity. RESULTS: The measurement in ANCT of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (5.416 ± 0.501 mU/mg protein and 6.350 ± 0.599 mU/mg protein, respectively) demonstrated that upper respiratory tract is capable of controlling the availability of ACh. In HNSCC, AChE and BChE activities dropped to 3.584 ± 0.599 mU/mg protein (p = 0.002) and 3.965 ± 0.423 mU/mg protein (p < 0.001). Moreover, tumours with low AChE activity and high BChE activity were associated with shorter patient overall survival. ANCT and HNSCC differed in mRNA levels for AChE-T, α3, α5, α9 and ß2 for nAChR subunits. Tobacco exposure had a great impact on the expression of both AChE-H and AChE-T mRNAs. Unaffected and cancerous pieces contained principal AChE dimers and BChE tetramers. The lack of nerve-born PRiMA-linked AChE agreed with pathological findings on nerve terminal remodelling and loss in HNSCC. CONCLUSIONS: Our results suggest that the low AChE activity in HNSCC can be used to predict survival in patients with head and neck cancer. So, the ChE activity level can be used as a reliable prognostic marker.

Oropharyngeal approach as a surgical alternative for cervical lymphatic malformation with airway compression.

Cervical lymphatic malformation is an infrequent benign congenital malformation of the lymphatic system, whose rapid growing capacity can compromise the airway. Here we present a 3-month-old male with severe respiratory impairment showing pharyngeal, cervical and mediastinal lymphatic malformation. Transoral surgery maintaining the mucosa allowed removal of numerous cystic lumps occupying the whole pharynx up to the pyriform sinus, surrounding the common carotid artery. Postsurgical MRI showed that the pharynx portion of the lymphatic malformation had disappeared. We conclude that the oropharyngeal approach is an alternative to the classical external surgery involving upper respiratory tract compression.