Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas.

OBJECTIVES: Aberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients. MATERIALS AND METHODS: Methylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level. RESULTS: The analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients. CONCLUSIONS: Our findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling. CLINICAL RELEVANCE: The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas.

The negative regulators of Wnt pathway-DACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival.

The deregulation of Wnt signaling has recently emerged as one of the drivers of head and neck cancers. This is frequently related to the methylation of several antagonists of this pathway. This study aimed at the assessment of the profile of methylation of Wnt pathway antagonists and the determination of the prognostic value of the methylation of selected genes in oral carcinomas. The methylation of DACH1, DKK1, LKB1, PPP2R2B, RUNX3, SFRP2, and WIF-1 was analyzed in 16 oral squamous cell carcinoma cell lines using the methylation-specific polymerase chain reaction. The methylation of selected genes was further analyzed in tumor sections from 43 primary oral carcinoma patients. The analysis of oral carcinoma cell lines showed very frequent methylation of SFRP2 and WIF-1 and also a less frequent methylation of DACH1 and DKK1. On the other hand, RUNX3 was methylated only in one cell line, while LKB1 and PPP2R2B were not methylated in any of the cell lines. The biallelic methylation of DKK1 correlated with the low level of expression of this gene. Further evaluation of the methylation of DACH1, DKK1, and WIF1 in a clinical patient group confirmed the frequent methylation of WIF1 and intermediate or low frequency of methylation of DACH1 or DKK1, respectively. Importantly, the methylation of WIF-1 correlated with shorter survival in oral cancer patients. Overall, the methylation of the antagonists of Wnt pathway is frequently detected in oral squamous cell carcinomas. The methylation of WIF1 may be considered a prognostic marker in oral cancers.

Long-term results of the Er-Yag laser used in stapes surgery.

Stapes surgery is performed using both conventional techniques and a variety of laser systems. The Er-Yag laser is a type of pulsation laser deemed by many to be the safest for ear surgery. The aim of this study was to assess the long-term effects of using the Er-Yag laser in stapes surgery and its impact on inner ear function. The study was conducted on 95 ears (48 right and 47 left) that had undergone Er-Yag laser-assisted stapedotomy. The follow-up time was at least 3 years. Pure tone audiometry was performed on all patients. The frequency ranged from 125 to 8,000 Hz. Air conduction and bone conduction were both assessed. Moreover, all patients had their stapedius reflex assessed and were given a Rinne test. The results were evaluated according to the Committee on Hearing and Equilibrium guidelines and then statistically analyzed using the Wilcoxon sequence pair test with a p value of <0.05. A decrease in the hearing threshold of 0.5, 1, and 3 kHz, for both bone and air conduction was observed for all patients (p < 0.0001). The Wilcoxon sequence pair test revealed a statistically significant correlation between the pre- and postoperative treatment mean air-bone gap values (p < 0.0001). No facial nerve paralysis was observed. No Er-Yag laser side effects were observed on inner ear function. The patients also had lower hearing thresholds. These observations demonstrate the usefulness of Er-Yag lasers in stapes surgery.

Prognostic factors in oral and oropharyngeal cancer based on ultrastructural analysis and DNA methylation of the tumor and surgical margin.

Oral and oropharyngeal cancers are characterized by relatively low 5- year survival rates due to many factors, including local recurrence. The identification of new molecular markers may serve for the estimation of prognosis and thus augment treatment decisions and affect therapy outcome. The aim of this study was to describe the morphological characteristics and the DNA methylation status of the CDKN2A,CDH1, ATM, FHIT and RAR- genes in the central and peripheral part of the tumor and the surgical margin and evaluate their prognostic significance. 53 patients with oral and oropharyngeal cancer were enrolled to the prospective study, and had been primarily treated surgically. Correlations between morphological data, hypermethylation status and clinicopathological data, as well as prognosis, were assessed. Nuclei polymorphism highly correlated with T stage (p < 0.0001), N stage (p < 0.046), and metastases to the lymph nodes pN (p < 0.004 ). Also, the number of cells in irregular mitosis correlated with T stage (p < 0.004), and highly with pN (p < 0.009). The significance of CDKN2A hypermethylation as a good prognostic factor was also established in the Kaplan-Meir test. The ultrastructural analysis showed that none of the examined tumors had homogenous texture and that resection margin specimens clean in HE stained tissue samples frequently contained single tumor cells or few cells in groups surrounded by connective tissue. This indicates the superiority of electron microscopy over standard histopathological analysis. Thus, a combination of such morphological examination with epigenetic parameters described herein could result in the discovery of promising new prognostic markers of the disease.

Variable course of progression of oral cavity and oropharyngeal carcinoma in young adults.

AIM OF THE STUDY: The main aim of this article is the epidemiological analysis of patients treated due to oral and oropharyngeal cancer, with a special interest in the group under the age of 40, evaluation of the differences in the clinical course of the disease as well as assessment of the treatment results, regarding the age of the affected individuals. MATERIAL AND METHODS: 523 individuals affected by oral and oropharyngeal cancer who were treated in the Otolaryngology and Laryngeal Oncology Department between 2000 and 2008. Precise analysis was performed on 360 out of 523 affected individuals, in whom full clinical status was determined; 13 patients were young adults. The retrospective analysis was created based on case histories, surgical protocols and emergency records. RESULTS: In young adults there is a markedly increased risk of organ involvement according to the Mann-Whitney U-test analysis (p = 0.044907). The probability of recurrence in the group of young adults is also much higher. Analysis of Kaplan-Meier test results indicated that the chance for the lack of recurrence within a 6-month period was 85.7%; however, the risk of recurrence increased, and after 12 months was equal to the arithmetic data (50%). CONCLUSIONS: Among young adults there is an increased risk of local recurrence following 12 months after surgical intervention. According to our observations, despite rapid progression and early recurrence in young adults (4/7) the prognosis for both groups is not statistically different.

[The HPV infection as an alternative to tobacco smoking way of head and neck tumors development--what are the implications for patients?]. / Infekcja HPV jako alternatywna wobec palenia tytoniu droga rozwoju nowotworów glowy i szyi--jakie ma znaczenie dla pacjenta?

It was established, that HPV virus (Human Papilloma Virus) is responsible for tumor induction in some anatomical regions of head and neck, mainly in palatine tonsils. The characteristics of HPV-related tumors as well as the course of the disease are definitely different compared to tobacco-smoking related tumors; patients HPV-positve have better prognosis - less patients develops recurrences and dies from the disease. There is no full compliance about patients' characteristics, although most indications concern "young adults" with their intensive sexual life. Because the course of HPV-related tumors is milder, there is a need to distinguish the cause of disease to carry on the therapy adjusted to the causative factor. This approach might help to select HPV-negative patients with severe course of disease to apply more aggressive chemotherapy.

[Retrospective analysis of the treatment failure of the oral cancer in Department of Otolaryngology and Clinical Oncology University of Medical Sciences in Poznan in the year 2000-2005]. / Retrospektywna analiza przyczyn niepowodzen w leczeniu nowotworów jamy ustnej i gardla w Klinice Otolaryngologii i Onkologii Laryngologicznej Uniwersytetu Medycznego w Poznaniu w latach 2000-2005.

AIM: Retrospective analysis of treatment results in the patients group with oral cancer treated in Department of Otolaryngology and Clinical Oncology K. Marcinkowski University of Medical Sciences in Poznar' between the years 2000-2005. The critical view of the cause of the failure. MATERIAL: The clinical date include: sex, age, stage of the tumor (TNM classification), histological grading, nodes status and 5-years follow up. The parameters were analysed regarding to history of the patients, operative books, outpatients documentation. All parameters were underwent statistical analysis using following tests: Kaplan-Meier, Wilcoxon regarding Gehan and chi2. Date for analysis was classified as ,,end feature" (death or lack of postoperative control) and ,,cut feature" (patient still under control). RESULTS: Between 2000 and 2005 263 patients were operated due to oral cancer. Only 144 undergo analysis. The rest of 108 patients were calculated as a treatment failure. The middle age was 63 years. There was statistical correlation between tumor stages T (p< or =0.00768), pathological N stage (p< or =0.07225) and 5 year survival. No correlation was found between age, extracapsular spread of the nodes and histopathological grading G and prognosis. In our group 5-years survival present 32% of the patients. CONCLUSIONS: The results of 5-years survival in our patients group are still unsatisfactory. The key lies probably on both side. The first the patients visited doctors still to late with significant advancement of the tumor and second we need better education, introduction of new technologies and shorter time for histological diagnosis and waiting list for post operative radiochemioterapy.

[The importance of postoperative care after functional endoscopic sinus surgery]. / Znaczenie postepowania pooperacyjnego w operacjach czynnosciowych nosa i zatok przynosowych.

INTRODUCTION: In this work we wish to emphasize the importance of postoperative care of patients who underwent FESS in ENT Department Medical University in Poznan. We feel that too little attention is still being paid to this treatment as we mostly focus on surgery. MATERIAL AND METHODS: Our observation are based on nine year experience in functional endoscopic sinus surgery. The analysis covers patients hospitalized in our Department from January 1998 to August 2007. The schedule of postoperative care has been presented. RESULTS: 1463 FESS operation were carried out in our Department from January 1998 to August 2007. Similar postoperative procedures were used with each patient. Full recovery of mucous membrane depended on a few parameters such as: if the patient underwent FESS for the first time, what kind of changes were observed: polips or chronic infection, as well as the method of surgery ("aggressive" versus "delicate"). Healing time ranged from 6 week to 3 month. CONCLUSIONS: The scheme of procedures employed comes useful in postoperative treatment after FESS.

[9-years results of the functional endoscopic sinus surgery in ENT department in Poznan--from microscope to four hands technique]. / 9-letnie doswiadczenia Kliniki Poznanskiej w chirurgii czynnosciowej zatok przynosowych--od mikroskopu operacyjnego do techniki czterech rak.

Surgical procedure is used in chronic rhinosinusitis and aims at restoring proper drainage and ventilation. For this reason the surgery of this region is referred to as functional and in English literature is termed as FESS. It supplanted classical method of Caldwell-Luc or Denker. In the study nine years experience in the Department of Otolaryngology, Head and Surgery University of Poznan in the treatment of chronic sinusitis has been presented. 1463 patients treated with FEES were analyzed. Moreover, the method of selecting patients for the surgery, the diagram showing surgeries performed step by step as well as a list of various surgeries and intraoperative complications were presented. This work is the first part of the study. In the other part the results of the treatment based on the questionnaires sent to patients will be presented.

Frequent methylation of DAB2, a Wnt pathway antagonist, in oral and oropharyngeal squamous cell carcinomas.

BACKGROUND: Aberrations in Wnt signaling pathway are related to the pathogenesis of head and neck carcinomas and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of the methylation of DAB2, which acts as a negative regulator of Wnt signaling, and correlate it with clinicopathological features in a group of oral cancer patients. MATERIAL AND METHODS: Forty nine patients with primary oral squamous cell carcinoma were enrolled in the study. DNA samples were isolated from surgical sections using phenol-chloroform extraction. Methylation-specific PCR was used to detect gene promoter methylation. RESULTS: The analysis of the occurrence of DAB2 promoter methylation in primary oral carcinomas indicated that the gene is methylated in 70% of cases. However, no correlation was found between its methylation and TNM staging or overall survival. CONCLUSIONS: Our findings corroborate that DAB2 is a frequent target of epigenetic silencing in oral carcinomas and may be potentially used for tumor detection.

Functional endoscopic sinus surgery (FESS) in unilateral sinus disease.

BACKGROUND: Unilateral sinus disease (USD) occurs in 23 % of all cases. It is believed that it is mainly associated with cancer development. Retrospective data from large rhinological centers show that the most common USD is chronic rhinosinusitis (CRS), followed by mycosis, inverted papilloma and finally cancer, but only in a small percent of cases. THE AIM OF THE STUDY: The analysis of USD in the group of patients who underwent FESS at the secondary referral center. MATERIAL AND METHOD: The retrospective study of patients treated for USD in the Department of Otolaryngology in the Provincial Hospital in Poznan between June 2014 and June 2016. The analysis includes age, sex, the localization of lesions, histopathological and microbiological results, an extension of the surgery and treatment results. RESULTS: Over the analyzed period of time, 415 FESS for chronic sinusitis were performed. In this group, 83 patients underwent surgery for USD. There were 35 women and 48 men.CRS was found in 48 cases, mycosis in nine cases, 12 patients were operated for non-malignant tumors, such as inverted papilloma (9), osteoma (2) and fibrosis tumor(1); seven patients had a choanal polyp and two of them had a foreign body in maxillary sinus - a tooth root lying loose. Four patients were diagnosed with a hypoplastic maxillary sinus and one patient suffered from frontal sinus pyocele. One side endoscopic opening of all sinuses was performed in the group with CRS, endoscopic medial maxillectomy was conducted in patients with inverted papilloma, and an isolated opening of the affected sinus was performed in the cases with mycosis. CONCLUSIONS: USD must be always suspected of malignant degeneration until proven otherwise. Endoscopic sinus surgery with the use of angled scope allows for the removal of even very extensive lesions. In our opinion, the extent of operation is determined by the nature of pathology. While extensive surgery is recommended in patients with inverted papilloma, a limited procedure should be performed in those with isolated mycosis.

[Use of the lymphoscintigraphy in detection of sentinel lymph nodes of the neck]. / Zastosowanie limfoscyntygrafii w wykrywaniu wartowniczych wezlów chlonnych w obrebie szyi.

Technique of the application of radioactive tracer to the primary tumor and lymphoscintigraphy with use of the stationary and handheld gamma probe was presented. Various types of the used radioactive tracers were characterized. Scintigraphical criteria for sentinel nodes recognition were discussed. Advantages and limitations of the use of lymphoscintigraphy for sentinel nodes detection were described. Necessity of further study to determine feasibility of sentinel nodes radiolocalization in stage N0 in head and neck cancer was pointed out.

[The sentinel node in cancer of the oral cavity, pharynx and larynx]. / Wezel wartowniczy w nowotworach jamy ustnej, gardla i krtani.

AIM OF THE STUDY: The evaluation of the importance of the prognostic of sentinel node biopsy in head and neck cancer with N0 neck. MATERIAL AND METHODS: Prospective study included 19 patients with squamous cell carcinoma of the oral cavity, pharynx and larynx without enlarged lymph nodes in ultrasound examination (N0). The study was carried out in ENT Department of Medical University in Poznan between 2001-2004. Each patient underwent lymphoscintigraphy after administration of radionuclide Technetium 99m (Nanocol). In case of detection of sentinel node, blue dye was injected into the tumour bed and dyed lymph nodes were removed. The specimens were evaluated histologically and immunohistochemically. The patients are still followed up. RESULTS: So far 19 patients were included in our study. The tumours were classified from T1 to T4. In each case sentinel nodes were located. Metastases in removed lymphnodes were found in 5 patients. In one of them regional recidive was observed after 5 month. In the other patients no changes were found in follow up examination. In 14 cases in histological examination no metastases were found in sentinel nodes. In this group in one case local recurrence was observed and in another two lymph nodes metastases were confirmed. In patients with positive sentinel node elective neck dissection was performed. So far immunohistochemical examination has not provided us with any vital information. In no case with negative sentinel node we found micrometastases with the use of cytokeratin. CONCLUSIONS: Based on our preliminary observation of the patients we have found that there is certain correlation confirming the fact that sentinel node may be reliable for the whole neck lymphatic system. Further clinical observation are needed based on a larger number of patients and longer observation period.

[Il-5 and il-6 in pathogenesis of chronic sinusitis: our experience]. / Rola IL-5 i IL-8 w patogenezie przewleklego niezytu nosa i zatok przynosowych--doswiadczenia wlasne.

The aim of the study was to appraise the level of interleukin 5, 8 in secretion from the nose in etiology of chronic inflammatory state of the nose and nasal sinuses. The group of 32 patients classified as group suffered from the inflammatory state of nasal sinuses described in the International Nose and sinuses Conference in Princeton, New Jersey 1993 was examined. The level of IL-5 and IL-8 with ELISA method was indicated and the cytological examination was carried out. In the material a predominance of neutrophils implying a bacterial etiology of illness was observed. Simultaneously the high level of IL 8 (13-1393 average 2.7 +/- 6.1) was indicated.

Comparison between 2 laser systems, Er-Yag and CO2, in stapes surgery.

OBJECTIVE: The aim of the study was to compare 2 laser systems, Er-Yag and CO2, in stapes surgery. STUDY DESIGN: The study design was retrospective. SETTING: The study was conducted at an academic tertiary referral center. PATIENTS: There were 88 women and 34 man in the analyzed group. The study was carried out on 142 ears: 52 on the right ear, 50 on the left ear, and 20 bilateral. Forty-seven ears underwent a CO2 laser-assisted stapedotomy, and 95 underwent Er-Yag-assisted stapedotomy; 23 left and 24 right ears were operated on using the CO2 laser. The Er-Yag laser was used in 48 right and 47 left ears. The follow-up time was at least 1 year. RESULTS: When the postoperative air-bone gap was compared with the preoperative air-bone gap for the 2 laser systems using the Student t test, as well as the Mann-Whitney U test, no statistical differences were found between the 2 groups, that is, with the use of Er-Yag and CO2 lasers. Also, no statistically significant differences were measured over all frequencies by the Student t test between preoperative and postoperative bone conduction in each group. CONCLUSION: To sum up, our observations have proven the usefulness of 2 laser systems: CO2 and Er-Yag lasers in stapes surgery. In both groups, a decrease in the hearing threshold was obtained.

[Stapedotomie with the use of CO2 laser--"one shot" technique]. / Stapedotomia z uzyciem lasera CO2--technika jednego strzalu.

INTRODUCTION: CO2 laser is used in stapes surgery due to good water absorption and quite optimal ablation of a bony structure without the influence of inner ear parameters. AIM OF THE STUDY: the assessment of the influence of CO2 - "one shot" laser on hearing results in the patients group with otosclerosis. MATERIAL AND METHOD: The study was carried out on a patients group after surgical treatment. The follow up time was at least 6 months. The hearing results were described according to the guidelines of the American Committee on Hearing and Equilibrium. The obtained results were statistically analysed with the use of the Wilcoxon sequence pair test. RESULTS: The CO2 - "one shot" laser has been used in Department of Otolaryngology in Poznan since July 2009. Using this system 101 operations were carried out to the end of December 2011. 54 patients were in the analysed group, there were 40 women and 14 men, the age range from 22 to 59. In the Wilcoxon sequence pair test there was a statistically significant correlation between the value of the hearing threshold in pre- and post-operative examinations at 0.5, 1, 2 and 3kHz for bone and air conduction. We found also a statistically significant correlation between the mean value of the air-bone gap before and after treatment. In the group after the surgery the cochlear reserved became closed or decreased (p<0.001). CONCLUSION: based of the hearing results we found great usefulness of CO2 - "one shot" laser in stapes surgery.

[The role of carbocystein in the treatment of sinusitis]. / Rola karbocysteiny w leczeniu zapalen zatok przynosowych.

Chronic sinusitis is one of the most common presenting complaints of all doctor visits in the United States and Europe, with more than 13% of people affected in any given year. This disease has a wide range of impact on communities. Patients with recurrent or chronic sinusitis report a deteriorative sense of general health and vitality, when compared to general population. In our Department we perform about 600 functional endoscopic sinus surgeries (FESS) per year. Chronic rhinosinusitis represents a spectrum of inflammatory and infectious processes concurrently affecting the nose and paranasal sinuses. Among chronic paranasal sinusitis one must single out paranasal sinusitis with and without polyps. In the paranasal sinusitis patomechanism the blockage of natural ostium plays one of the most important roles. The closure of sinus proper ventilation passages leads to the triggering of many pathological occurrences within mucous membrane of this region. The treatment of paranasal sinusitis is diversified and involves a surgical procedure as well as anti-inflammatory and antiallergic drugs (medications) and mucolytics. Its purpose is to clear the nose through the elimination of bacterial infection, liquidating and removal of lying discharge and the restoration of the proper muco-ciliary transportation, and through this the improvement of local condition and faster recovery. In this work the usage of carboxycysteine to treat paranasal sinus conditions has been presented.

Laminin expression in advanced laryngeal squamous cell carcinoma does not correlate to neck metastases.

Laminins are a family of glycoproteins that consist of one heavy alpha chain and two light beta and gamma chains. The laminin molecule is a major component of the basement membrane and plays an important roles in cell differentiation, adhesion, and migration. It has been reported that laminin is strongly expressed at the invasive front of the tumor and plays an important role in forming the metastases. The aim of the study was to assess the importance of laminin expression in a group of patients with laryngeal carcinoma and neck metastases. The study was carried out on 70 patients with squamous cell carcinoma of the larynx treated at the ENT Department University of Medical Sciences in Poznan. The clinical data consisted of sex, age, stage of the tumor, and histological and immunohistochemical studies. The average time of the follow-up was 3 years. The immunohistochemical study was performed using formalin-fixed and paraffin-embedded tissue sections. Monoclonal mouse anti-human laminin (DAKO, code no. MO638) antibodies were used for immunohistochemistry. To evaluate the laminin staining, a four-point grading system were used: score 0, continuous; score 1, loss of staining <10%; score 2, loss of staining <50%; score 3, loss of staining >50%. The correlation between staining intensity of the laminin and the presence of neck metastases (classified as N-positive "N+" and N-negative "N-"neck) was calculated. All parameters underwent statistical analysis. The patients with advanced clinical disease dominated in our material. Most of the tumors were classified as T3 and T4. A total of 36 patients had metastases to the regional lymph nodes. Positive laminin staining was observed in 62 cases. There was no correlation between laminin staining and occurrence of neck metastases in our studied group (30 N+ and 32 N-). The gravity level in Wilcoxon test was at P < 0.000001 and in Spearman rank order correlation was statistically not significant (P > 0.09).

Cyclin D1 gene (CCND1) polymorphism and the risk of squamous cell carcinoma of the larynx.

Cyclin D1 is one of the key proteins involved in cell cycle control, and it is believed that its overexpression may be connected with tumorigenesis. A reason for cyclin D1 deregulation may be connected to a common G870A polymorphism at codon 242 in exon 4 of the CCND1 gene. This single nucleotide substitution, localized in the conserved splice donor site between exon 4 and the intron 4 boundary, might modulate the frequency of alternative splicing. It has been postulated that the A allele results in a higher level of mRNA (transcript b) encoding a protein with an altered C-terminal domain. The influence of CCND1 G-->A polymorphism for the risk of cancer and the prognosis of patients with different types of solid tumors has already been suggested. This study was conducted to investigate the association between the cyclin D1 gene polymorphism and laryngeal cancer risk, as well as the clinical outcome. We also examined the relationship between genotype/allele distributions and the cyclin D1 expression profile. The genotyping study was done using the PCR-RFLP method in 63 patients with larynx cancer and 102 healthy controls. The heterozygotic genotype GA as well as a combination of GA and AA genotypes were associated with an increased risk of larynx cancer compared to the GG genotype (OR =3.02; P =0.004 and OR =2.52; P =0.013, respectively). The A allele frequency was higher in cancer cases (0.484) than in controls (0.416) that were connected with a slightly increased risk of cancer development (OR =1.34); however, the difference was not significant. The AA genotype was associated with an early cancer onset compared to the GG genotype (median age: 51.5 and 63.0 years, respectively). We also demonstrated that the AA genotype was associated with the occurrence of lymph node metastases (OR =3.26) and a higher level of cyclin D1 overexpression. These results suggest that the CCND1 A allele may be a genetic factor that modulates the risk of larynx cancer development, and it may also have an effect on tumor biology and disease prognosis.