Population attributable risk of tobacco and alcohol for upper aerodigestive tract cancer.

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe.

Predicting postoperative morbidity and mortality by model for endstage liver disease score for patients with head and neck cancer and liver cirrhosis.

BACKGROUND: The purpose of this study was to evaluate the Model for Endstage Liver Disease (MELD) scoring system for predicting the morbidity and mortality of patients with head and neck cancer with liver cirrhosis undergoing tumor resection with microsurgical free-tissue transfer. METHODS: Between January 2000 and December 2008, 3108 cases were retrospectively reviewed. RESULTS: There were 59 men and 2 women enrolled in this study. Preoperatively, 31 and 30 patients were classified as having lower (<9.73) and higher (>9.73) MELD scores, respectively. Patients with higher MELD scores had significantly more postoperative medical morbidities including pulmonary complications and gastrointestinal bleeding. The mortality rate was also significantly higher for higher MELD scorers (23.3% vs 3.2%; p = 0.026). By logistic regression model, preoperative MELD score was a significant predictive factor for morbidity and mortality in multivariate analysis. CONCLUSION: MELD score could be used to predict morbidity and mortality for patients with head and neck cancer with liver cirrhosis undergoing tumor resection with microsurgical free tissue transfer.

Formaldehyde and cancer risk: a quantitative review of cohort studies through 2006.

BACKGROUND: Occupational exposure to formaldehyde has been associated with excess risk of nasopharyngeal and selected other cancers. PATIENTS AND METHODS: We reviewed and pooled the results of cohort studies published through February 2007. RESULTS: There were 5651 deaths from all cancers observed in six cohorts of industry workers and six of professionals, with a pooled relative risk (RR) of 0.95 for industry workers and of 0.87 for professionals. Nine deaths from nasopharyngeal cancer in three cohorts of industry workers yielded a pooled RR of 1.33, which declined to 0.49 after excluding six cases from one US plant. The pooled RR for lung cancer was 1.06 in industry workers and 0.63 in professionals. Corresponding values were 1.09 and 0.96 for oral and pharyngeal, 0.92 and 1.56 for brain, 0.85 and 1.31 for all lymphatic and hematopoietic cancers, and 0.90 and 1.39 for leukemia. CONCLUSIONS: Comprehensive review of cancer in industry workers and professionals exposed to formaldehyde shows no appreciable excess risk for oral and pharyngeal, sinonasal or lung cancers. A non-significantly increased RR for nasopharyngeal cancer among industry workers is attributable to a cluster of deaths in a single plant. For brain cancer and lymphohematopoietic neoplasms there were modestly elevated risks in professionals, but not industry workers.

[Effects of nicotine with special consideration given to tumorigenesis in the head and neck region]. / Effekte von Nikotin unter besonderer Berücksichtigung der Tumorentstehung im Kopf-Hals-Bereich.

BACKGROUND: Tumorigenesis is based on initiation, promotion, and progression, whereas tobacco smoke is a decisive predisposing factor for squamous cell carcinomas of the upper aerodigestive tract. A variety of tobacco smoke compounds is known to potentially initiate tumors, but the alkaloid nicotine is generally considered to induce addiction only. However, there is growing evidence that nicotine may also contribute to early stages of tumorigenesis. In the present study, a possible direct genotoxic potential of nicotine is investigated. MATERIAL AND METHODS: Lymphatic tissue of the tonsilla palatina of eight donors was harvested during surgery and incubated with nicotine. DNA damage was measured with the comet assay. RESULTS: Genotoxic effects of nicotine could be demonstrated. DISCUSSION: The results suggest a direct contribution of nicotine to tumor initiation and carcinogenesis.

[Does nicotine add to the carcinogenic strain of tobacco smoke?]. / Trägt Nikotin zur Krebsentstehung im oberen Aerodigestivtrakt bei?

BACKGROUND: It is accepted that nicotine in tobacco smoke causes addiction via nicotinic acetylcholine receptors in the central nervous system. For a long time, the tumorigenic potential of smoking was attributed to compounds other than nicotine. However, more recently data have accumulated which suggest that nicotine may add to the cancer risk by stimulating cellular growth via non-neuronal acetylcholine receptors, by suppressing apoptosis, and by inducing angiogenesis not only in atheromatous plaques but also in tumors. In the present study the possible direct genotoxic effects of nicotine on DNA were investigated in human target cells of carcinogenesis in the upper aerodigestive tract. PATIENTS AND METHODS: Human nasal mucosa, lymphatic tissue of the palatine tonsils, supraglottic epithelium of the larynx, and peripheral lymphocytes were exposed to rising concentrations of nicotine. DNA damage was investigated by alkaline single-cell microgel electrophoresis (Comet) assay. Cytotoxicity was assessed by trypan blue exclusion. RESULTS: Nicotine induced dose-dependent DNA damage in all cell types at low cytotoxic concentrations that allowed viabilities well above 80%. The lowest nicotine concentrations eliciting a significant increase in DNA migration were 1 mM for tonsillar cells and 0.25 mM for all other cell types. CONCLUSION: Nicotine induces genotoxic effects in human target cells of carcinogenesis in the upper aerodigestive tract at relevant concentrations. Thus, nicotine may contribute directly to tumor initiation resulting from smoking.

[Genotoxic effect of PCP and lindane on human epithelial tonsil cells]. / Genotoxische Wirkung von Pentachlorphenol und Lindan((R)) auf humane Tonsillenschleimhautepithelien.

BACKGROUND AND OBJECTIVE: Experimental and epidemiological studies have provided evidence that pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (lindane) may pose a potential carcinogenic risk for human epithelial cells of the upper aerodigestive tract. In the past, these two substances have been used for military and nonmilitary purposes, e.g., for impregnation of textiles and uniforms. In this study, we investigated the genotoxic effect of PCP and lindane on human mucosal tissue from the tonsils. METHODS: In epithelia obtained from the tonsillar mucosa removed during surgery, cell viability was evaluated by trypan blue staining. The specimens were incubated for 60 min with PCP (0.3, 0.75, and 1.2 mM) and lindane (0.5, 0.75, and 1.0 mM). The induction of DNA damage (single- and double-strand breaks) caused by PCP and lindane was measured using single-cell microgel electrophoresis. Evaluation was performed with an image analyzer enhanced by fluorescence microscopy. RESULTS: After exposure to PCP and lindane, strong genotoxic effects are apparent. The DNA migration rose from 26 micrometer in the control solution up to nearly 90 micrometer after incubation with PCP and lindane ( p<0.0001). CONCLUSIONS: This study could demonstrate for the first time genotoxic effects of PCP and lindane on human tonsillar epithelium. It has to be considered that chronic exposure to both agents might increase the risk for cancer of the upper aerodigestive tract.

[The single cell microgelelectrophoresis technique in ecogenotoxicology]. / Stellenwert der Einzelzell Mikrogelelektrophorese in der Okogenotoxikologie.

BACKGROUND: The development of carcinoma in the upper aerodigestive tract is often associated with exposure to xenobiotics. Therefore, the identification of such tumor initiating substances is relevant. Most genotoxicity test systems require mammalian cells, human lymphocytes or cell cultures to detect genotoxicity caused by carcinogens. The single cell microgelelectrophoresis technique (Comet assay) is presented, being a sensitive method, identifying DNA strand breaks, alkali labile sites and DNA repair in human epithelial cells of the upper aerodigestive tract. It is compared to other common techniques for the identification of genotoxic damage. Future applications and contributions of the method are introduced. GENOTOXICITY TEST SYSTEMS: Using the alkaline microgel electrophoresis assay, freshly isolated single epithelial cells are incubated with xenobiotics causing DNA strand breaks and alkali labile sites. Data are examined using a digital computer analysis. The method is described for the application of epithelial cells of the upper aerodigestive tract and compared to other procedures for the monitoring of genotoxicity. These are the Ames test identifying mutagenicity in bacteria, the sister chromatid exchange and the micronucleus test demonstrating genomic instability in lymphocytes and cultured mammalian cells. CONCLUSIONS: The microgel electrophoresis technique is a sensitive method to detect genotoxic effects and DNA repair in human epithelia of the upper aerodigestive tract. The assay offers considerable advantages to other common genotoxicity tests. However, combining of the Comet assay with mini organ cultures allows to use repetitive incubations with xenobiotics. Furthermore, signalling selected chromosomal material by the combination of the assay with the fluorescence in situ hybridisation, DNA-damage and -repair mechanisms within comets can be identified.

[Genotoxic effect on human mucous membrane biopsies of the upper aerodigestive tract]. / Genotoxische Wirkung auf menschliche Schleimhautbiopsien des oberen Aerodigestivtraktes.

BACKGROUND: In numerous epidemiologic studies, environmental and occupational substances such as sodium dichromate (Na2Cr2O7), benzo[a]pyren (B(a)P), and N'nitroso-diethanolamine (NDELA) have been shown to be of potential carcinogenic risk on human epithelial cells in the upper aerodigestive tract. METHODS: Using the alkaline microgel electrophoresis technique (comet assay). mucosal cells isolated from biopsies of the upper aerodigestive tract (nose, paranasal sinuses, mouth, pharynx, larynx, and tonsils) were used to analyze target sites for different genotoxic substances and specific sensitivities of each donor. The cells were freshly isolated by enzymic digestion. 0.5-1 x 10(6) cells per donor were obtained with viabilities between 80-100%. After in vitro incubation, the cells were subsequently subjected to the single cell microgel electrophoresis assay. Results were evaluated regarding the personal history of each donor, focusing on previous exposure to tobacco, alcohol, and occupational compounds. RESULTS: Na2Cr2O7 induced strong genotoxic damage in the nasal and paranasal sinus epithelia as well as in mucosa cells of the larynx. NDELA caused significant damage in mouth cavity epithelia and showed also to be harmful towards mucosa of pharynx and larynx. B(a)P induced fewer DNA strand breaks in mucosal cells of mouth, pharynx and larynx. Significant differences between individuals were apparent for tissue samples from different donors. The genotoxic damage induced in cells of donors with a history of chronic alcohol consumption was significantly higher than in cells of patients without chronic abuse of alcohol. CONCLUSIONS: The data shows that DNA damage in human epithelial cells of the upper aerodigestive tract induced by environmental and occupational substances can be demonstrated using the microgel electrophoresis technique. The influence of chronic alcohol consumption on the genotoxic effects of substances such as NDELA and B(a)P showed the importance of evaluating preexisting compounding factors.

[Medical ENT endoscopic studies in the iron and steel industry]. / HNO-ärztliche endoskopische Untersuchungen in der Eisen- und Stahlindustrie.

461 chromium- and nickel-exposed steelworkers were otolaryngologically examined by endoscopy. Besides chronic inflammatory diseases of the ear, nose and paranasal sinuses, the clinical diagnosis of leukoplakia and hyperplastic laryngitis was made for 30 workers. In no case a lesion suspicious of cancer was found. Office staff showing no such occupational risk factors served as the control group. It was found that in both groups smoking has to be assumed as the decisive factor for the development of chronic inflammation and precancerous changes in the oral cavity and the larynx.

Carcinogenicity of diallylnitrosamine following intragastric administration to Syrian hamsters.

Single and multiple intragastric doses of diallylnitrosamine [(DAN) CAS: 16338-97-9] administered to Syrian golden hamsters induced tumors, primarily of the respiratory tract, in which the nasal cavity epithelium was the preferred site. When compared to the effect of DAN after subcutaneous administration at equal doses, the incidence of respiratory tract tumors was lower but that of hepatic tumors was higher, suggesting partial metabolism of DAN in the liver. Comparative metabolic and mutagenesis studies in BD IX rats (which reportedly are refractory to the carcinogenic effects of DAN), in Wistar rats, and in Syrian hamsters showed that a greater proportion of orally administered DAN was exhaled by both rat strains (12-19%) than by hamsters (2-4%). The activity of the microsomal fraction of the hamster liver for metabolizing DAN to allyl alcohol was about 10 times higher than that in rats, whereas no significant species differences were found with the cytosolic fraction. Pretreatment of animals with phenobarbital (PB) or pregnenolone-16 alpha-carbonitrile (PCN) did not influence either microsomal or cytosolic enzyme activities in hamsters, whereas about a tenfold increase in enzyme activities was seen after pretreatment with PB in both rat strains and following PCN in Wistar rats. Moreover, in bacterial mutagenesis assays, hamster liver microsomes were twice as active as those in BD IX rats. The results are discussed in relation to the carcinogenicity of DAN in rats and hamsters.