José Manuel Aguirre-Urizar

Oral cancer and polymorphism of ethanol metabolising genes

Oral cancer is the sixth most common cancer worldwide and a major health problem in some parts of the world. Epidemiological studies have shown that habitual alcohol consumption could be a risk factor in oral carcinogenesis, although the true involvement of alcohol is unknown. Via alcohol dehydrogenase (ADH) and cytochrome P450 oxidase (CYP) alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Subsequently, and during the metabolizing process, acetaldehyde becomes acetate by acetaldehyde dehydrogenase (ALDH). Therefore, acetaldehyde levels are determined mainly by the action of ADH, CYP and ALDH. Recently, several studies have found that certain polymorphisms of genes encoding these enzymes confer a higher or lower metabolic activity and therefore different risk for certain malignancies such as oral cancer. In this review, we analyze the polymorphisms of alcohol metabolising enzymes in relation susceptibility to an oral cancer.

Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders

OBJECTIVES Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. STUDY DESIGN Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. RESULTS All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. CONCLUSIONS Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism.

Primordial odontogenic tumour: clinicopathological analysis of six cases of a previously undescribed entity

To describe the clinicopathological and immuno‐histochemical features of six tumours that do not fulfil the criteria of any of the currently classified odontogenic tumours.

Overexpression of cyclooxygenase-2 as a biomarker in different subtypes of the oral lichenoid disease

OBJECTIVE Oral lichenoid disease (OLD) includes a number of chronic inflammatory processes including oral lichen planus (OLP) and oral lichenoid lesions (OLL) with controversial diagnosis and prognosis. Cyclooxygenase-2 (COX-2) is a key enzyme for inflammatory processes and cellular proliferation. Its overexpression in some premalignant chronic inflammatory diseases and malignant neoplasias could point to its potential as a prognostic factor. The aim of this study was to analyze the COX-2 expression in different subtypes of OLD because of its potential to be a marker of altered behavior. STUDY DESIGN Forty-four samples from OLD patients were studied (30 females and 14 males) and classified according to their clinical (C1: only papular lesions/C2: papular and other lesions) and histological features (HT: OLP typical/HC: OLP compatible) according to published criteria. Standard immunohistochemical procedure was performed for COX-2 expression and a comparative and descriptive statistical analyses were performed. RESULTS Epithelial COX-2 overexpression was observed in 24 (54.5%) cases (C1: 13 [54.2%]/C2: 11 [45.8%], HT: 9 [37.5%]/HC: 15 [62.5%], P = .032). Inflammatory COX-2 overexpression was observed in 14 (31.8%) cases (C1: 6 [42.9%]/C2: 8 [57.1%], HT: 4 [28.6%]/HC: 10 [71.4%], P = .032). CONCLUSION Differences in COX-2 expression in subtypes of OLD may distinguish cases with a higher premalignant potential.

Role of cytochrome P‐450 genetic polymorphisms in oral carcinogenesis

Oral cancer is one of the most frequent head and neck cancers, and epidemiological studies have shown that smoking is a major risk factor in this pathology. However, as not all smokers develop oral cancer, some individuals must be more susceptible to develop this disease. This individual susceptibility has been related to different genetic variants in metabolizing enzymes. The cytochrome P-450 (CYP) family of enzymes metabolizes tobacco-related carcinogens producing reactive metabolites, which could cause DNA damage. Because of their functional role in the metabolism of tobacco-related compounds, the genetic polymorphisms found in the genes that code for CYP enzymes have been suggested to modulate oral cancer risk and contribute to individual susceptibility. In this review, we analyze and update the available evidence in the literature regarding the polymorphisms of CYP genes in relation to the susceptibility of developing oral cancer.

Ancient Schwannoma of the hard palate : an uncommon case report and review

Schwannoma or neurilemmoma is an infrequent benign tumor in the oral cavity that originates from the Schwann cells on the neural sheath of the peripheral nerves. Schwannomas are frequently located in the soft tissues of head and neck region, but only a 1 to 12% of them are located in the oral cavity. Some histological variants of schwannoma have been described including the cellular, plexiform, epithelioid, ancient, and melanocytic types. The “ancient schwannoma” is an uncommon variant of this tumor that shows specific histological characteristics, and is rare in the oral cavity with less than 15 cases described on the literature. Most of them were located in the tongue or in the floor of the mouth, being the hard palate an extremely rare localization. We present a new clinical case of an ancient schwannoma with a long time of evolution, arising from the nasopalatine nerve, and located in the hard palate of a 35 year old female. We also review the main clinical and histological characteristics of this pathology. Key words:Ancient schwannoma, neurilemmoma, palate, schwannoma.

Cytometric analysis of oral scrapings of patients with oral lichen planus.

A. Acha‐Sagredo, Y. Jiménez, J. V. Bagán, M. A. Echebarria‐Goicouria and J. M. Aguirre‐Utric analysis of oral scrapings of patients with oral lichen planus

Caries and Candida colonisation in adult patients in Basque Country (Spain)

Candida albicans is one of the most frequent pathogens of the oral cavity, as a major cause of opportunistic disease. Moreover, Candida could be a cofactor of common oral diseases, such as dental caries. The aim of this study was to analyse the oral yeast colonisation in adults with dental caries and to evaluate its relationship with this clinical entity. We studied 190 patients distributed into controls (58 patients) and patients with caries (132 patients). Oral samples were collected by oral rinse and cultured in a chromogenic agar. C. albicans was the most prevalent species isolated from oral specimens in both groups. Patients with caries had a greater Candida colonisation (74 patients, 56.1%), than persons without caries (18 patients, 31%, P < 0.01). Patients with caries were significantly more colonised by non‐C. albicans species than individuals without caries (P = 0.006). Moreover, the diversity of Candida species was richer in patients suffering from caries. The odds ratio of the colonisation of patients with caries was 3.144 (95% CI 1.525–5.478). There is a significant clinical correlation between dental caries and oral Candida colonisation in adults.

Root resorption caused by a maxillary sinus mucocele: a case report

A maxillary sinus mucocele is an infrequent but benign lesion that develops from the obstruction of a seromucous glandular duct of the maxillary sinus mucosa. This clinical entity is generally asymptomatic and self-limited. Mucoceles are described as rounded dome-shaped soft tissue masses frequently located on the floor of the maxillary sinus. In this paper, we present a case of a slightly radiopaque well defined shadow arising from the left maxillary sinus floor that produced the root resorption of the upper second left molar. After the surgical removal of the lesion through a Caldwell-Luc approach, histologic study confirmed the initial diagnosis of mucocele. This case report emphasizes the need of clinical and radiologic follow-up to detect any complications associated with these benign lesions, because, in rare occasions, they can show an aggressive growth pattern.

Polymorphisms in alcohol and tobacco metabolism genes in head and neck cancer in the Basque Country

BACKGROUND The Basque Country has one of the highest rates of head and neck squamous cell carcinoma (HNSCC) in Europe, although tobacco and alcohol consumption are not high when compared to other European countries where HNSCC incidence is lower. Our aim was to determine the role of genetic variation with regard to the metabolism of alcohol and carcinogens from tobacco smoke in the Basque Country. METHODS Fourteen polymorphisms in alcohol or tobacco metabolism genes were genotyped in 84 HNSCC patients and 242 healthy individuals from the Basque Country. RESULTS ADH1B histidine allele (rs1229984), CYP2E1 rs3813867 heterozygous genotype, and GSTT1 deletion conferred protection against HNSCC (OR: 0.318 [0.04-0.75], OR: 0.13 [0.02-0.94], and OR: 0.12 [0.02-0.60], respectively) while GSTP1 (rs1695) Val/Val genotype was related to an increased risk (OR: 4.12 [1.11-15.31]). Regarding alcohol and tobacco habits, GSTT1 deletion was associated with tobacco usage, while the 3 polymorphisms tested in ALDH2 were associated with alcohol consumption. However, genotypic distributions of these 7 SNPs did not differ from those observed for other Caucasian populations where HNSCC incidence is lower. CONCLUSIONS The identified genotypic variations in alcohol and tobacco metabolizing genes only by themselves do not seem to be responsible for the higher incidence of HNSCC observed in the Basque Country.