Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients.

OBJECTIVE: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. METHODS: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. RESULTS: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. CONCLUSION: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.

The combined effects of single-nucleotide polymorphisms, tobacco products, and ethanol on normal resting blood mononuclear cells.

INTRODUCTION: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. METHODS: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. RESULTS: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 µM nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. CONCLUSIONS: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas--a questionnaire survey in the Nordic countries.

BACKGROUND: Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. METHODS: A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). RESULTS: All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. CONCLUSION: Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.

Cancer of the parotid gland; long-term follow-up. A single centre experience on recurrence and survival.

BACKGROUND: The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival. PATIENTS AND METHODS: At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume. RESULTS: The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s. CONCLUSIONS: Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

1-[11C]-acetate PET imaging in head and neck cancer--a comparison with 18F-FDG-PET: implications for staging and radiotherapy planning.

PURPOSE: The aim of this study was to evaluate the feasibility of using 1-[(11)C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using (18)F-fluoro-2-deoxy-D: -glucose (FDG) PET. METHODS: Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart. Diagnostic CT or MRI was performed in all patients. The image data sets were analysed both visually and semi-quantitatively. All primary tumours and metastases were delineated automatically by using the 50% threshold of maximum radioactivity corrected for background. The mean standardised uptake value (SUV) and the tumour volumes were evaluated and compared. RESULTS: All ten primary tumours were detected by ACE-PET, while nine primaries were detected by FDG-PET and CT and/or MRI. The ACE SUV tended to be lower than the FDG SUV (5.3+/-2.7 vs 9.6+/-7.0, p=0.07). The tumour volumes delineated with ACE were on average 51% larger than the FDG volumes (p<0.05). ACE-PET identified 20/21 lymph node metastases, while only 13/21 lesions were detected by FDG-PET and 16/21 lesions by CT or MRI. CONCLUSION: ACE-PET appears promising for the staging of head and neck cancer. The biological information provided by both FDG and ACE must be carefully validated before it can be used in clinical routine for radiation treatment planning. More studies are needed to evaluate the differences in volumes and to confirm the clinical potential of both FDG and ACE-PET, especially in radiotherapy.