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According to epidemiological data head and neck cancers constitute for 12% of all malignancies in the world. It is estimated that a total of 400 000 cases of the mouth and throat and of 160 000 cases of laryngeal cancer, 300 000 people die each year. History of head and neck cancers developed and underwent many changes at the turn of the century. Treatment, pathogenesis and possessed state of knowledge on the subject has changed. Starting from the ancient times there were texts on how to treat and examine patients. The Edwin Smith and Ebers Papyrus are two of the oldest medical documents describing the treatment of cancer patients. Hippocrates was the first person who used the word "cancer" and probably he was the first who divided the tumors into benign and malignant. In a document known as the Doctrine of Hippocrates he described skin cancer and cancer treatments. Over the next centuries, medical science did not develop because of religious concerns about autopsy and surgical procedures. The 17th century is a period in which there were a lot of new information about how to treat such oral cancer. Cancer of the tongue was removed by cauterization, which in the 18th century was replaced by the use of surgical instruments. In the same age glossectomy has been accepted as the treatment of choice performed in the treatment of cancer. The 19th century brought a major breakthrough in the treatment of surgical, diagnostic, anesthetic techniques and understanding of the pathological mechanisms. Histological evaluation of tumors has become mandatory and standard practice in the assessment of cancer. Laryngectomy and neck lymph nodes removal has become commonplace. Modified Radical Neck Dissection (MRND), became popularized as another cancer treatment technique. Describing ways to treat cancer, radiotherapy can not be ignored - there are several new techniques such as Intensity Modulated Radiotherapy (IMRT) and hypofractionation currently used. Chemotherapy and the introduction of many new drugs have changed the outlook for patients suffering from cancer. Recently there are expectations about the targeted therapy, especially in medicaments blocking epidermal growth factor receptor (EGFR).

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.

Cigarette smoking and excessive alcohol drinking result in the rise of numbers of patients suffering from the head and neck cancer. Addiction to any of these stimulants carry a risk of developing a cancerogenesis process. Using them simultaniously lead not to a summary of each of those risks but multiplies them. Scientific research also indicates the important difference in the incidence of cancer in people who have never smoked cigarettes or drunk alcohol in comparison to those, whose exposure to these stimulatns was longterm - in such case, the former group had a lower percentage of developing the disease. Human body burdened with the ongoing cancer shows disturbances on various levels of the system. One of such disturbances is change of the concetration levels of physiological metals, such as calcium, magnesium, iron, copper, zinc or mangenese. They play key roles in maintaing the hormonal and ionic stability, they act as cofactors in many enzymes in metabolic processes. Diagnostic research of any deviations in levels of those essential elements enables a full estimation of a patient condition. The aim of this study was physiological metal levels evaluation in different kinds of biological material in patients with tumors of larynx, salivary glands and oral cavity and tongue. Hair and nail samples were used as examples of alternative material, beside the serum samples, which is a standard material and often used. Subjects were patients of Otolaryngology and Laryngological Oncology Clinic of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu) and The Head and Neck Surgery Ward of The Greater Poland Cancer Centre in Poznan. Subjects were 41 men and 18 women with tumors of larynx, salivary glands and oral cavity and tongue. The control group consisted of patients from the Otolaryngology and Laryngological Oncology Clinic of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu), The Head and Neck Surgery Ward of The Greater Poland Cancer Centre in Poznan and patients of Department of Endocrinology, Metabolism and Internal Medicine of Poznan University of Medical Sciences (Samodzielny Publiczny Szpital Kliniczny nr 2 im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu) and Department of Conservative Dentistry and Periodontology Poznań University of Medical Sciences. They gave answers to the questionnaire concerning smoking habits, alcohol consumption and dietary habits, Then the samples of their serum, hair and nails were collected. After careful preparations the biological material has underwent the process of digestion, and then calcium, magnesium, iron, copper, zinc, mangenese were determined quantitatively using the method of ICP-MS. Profile of the patients who took part in the research displayed a strong correlation between tobacco smoking with alcohol drinking and appearance of larynx, salivary gland and oral cavity and tongue cancer as well as between exclusively tobacco smoking and appearance of these types of cancer. There is a higher incidence of larynx, salivary gland and oral cavity and tongue cancer when there is a deficiency of grain products or fibre in everyday diet. A higher level of calcium, magnesium, iron and manganese was found in patients' hair and nails who suffered from salivary gland cancer. According to applied Chemometric Analysis of Principal Component 1 - concentrations of iron, copper and manganese with magnesium and zinc in patients' nail samples showed strong correlation between measured variables. In patiens' hair samples measured correlation between variables was decreased - concentrations of calcium and magnesium as well as of iron and manganese were highlighted as two groups of variables which showed some correlation in this type of biological material. Further research is required to indicate which of alternative biological materials - hair or nail samples - in relation to serum, would provide a better evaluation of physiological metal levels.

Statistics concerning tobacco smoking confronted with cancer epidemiology indicates that only a minority of smokers develops terminal cancer. To much extent it could be explained by genetic polymorphism responsible for a variable risk to develop cancer and its further progression. Then, a comparative analysis of the data concerning cancer deaths regarding a decline of smoking in developed countries unravels other factors previously not considered to represent carcinogenic agents. Human papilloma virus (HPV) could serve as an example of such agent exerting adverse health effects once attributed only to tobacco.

Initiation and progression of laryngeal cancer is associated with tobacco smoking and abusing of strong alcoholic beverages. A significance of genetic factor, although not defined sufficiently yet has been raised as well. The studies were focused on an influence of AHR gene polymorphism on survival of squamous cell carcinoma laryngeal subjects. The study material was 65 archival DNA samples analyzed by RLP-PCR. The samples varying with electrophoretic mobility were DNA sequenced. In the study group 9 heterozygotic variants Arg554Lys (codon 554) were detected. One case was a carrier of two other mutations in codon: 490 (1468 A > G) and 570 (1708 G > A). Survival time, metastasis and occurrence of second primary tumors were compared in carriers of wild type and Arg554Lys variant AHR. Preliminary results indicate for a necessity of further studies as until now the study group is too small to find a conclusive association.

Tumour suppressor gene TP53 is a subject of frequent lesions and mutations in a majority of cancer types that is followed by its dysfunction in regulation of cell proliferation, apoptosin and DNA repair. Mutation profile reflects the presence of mutagen-vulnerable sites (including tobacco smoke carcinogens) in its structure. A number of mutations in tobacco smoke-associated cancers are higher than in other types. Particularly, G > T mutation is recognized a signature to benzo(a)pyrene exposure. Further, a mutation profile is dependent on cancer anatomic localization and histological type. There were put forward suggestions concerning estimation of cancer risk and disease prognosis basing of TP53 gene status and expression. The protocols of gene therapy involving TP53 gene are still not satisfactory.

Laryngeal cancer in Poland is characterized by high levels of morbidity and mortality. The main risk factors for the larynx cancer are alcohol drinking and tobacco smoking. In contrary to well established tobacco-related evidence for an increased risk of larynx cancer, alcohol-related mechanisms of carcinogenesis remain unknown. Nevertheless the effect of alcohol is modulated by polymorphisms in genes encoding enzymes for ethanol metabolism. Hence we investigated the ADH1C *1 genotype and allele frequency in a group of 102 larynx cancer patients with heavy alcohol consumption recruited from the Department of Otolaryngology and Laryngological Oncology of the University of Medical Sciences in Poznan. The data were compared with 112 non-cancer age-matched individuals consuming similar amounts of ethanol. Blood samples were used for analysis of restriction fragment length polymorphism. DNA was isolated from the whole blood leucocytes and PCR with specific primers was used to amplify polymorphic region of rs698 in the ADH1C gene. The method was based on allele detection by Sspl restriction enzyme digestion and after the incubation with enzyme, samples run on an electrophoresis. The statistic analysis was performed to calculate Odds Ratio (ORs), 95% confidence intervals (CIs) and significance. Results suggest a slightly increased risk of larynx cancer for individuals who have inherited the ADH1C *1 allele (rs 698), however they did not reach the level of statistic significance.

The article presents the current techniques used for the identification of genes involved in tobacco smoke-associated cancers. The focus is set on the techniques derived from the conventional cytogenetics and includes fluorescence in situ hybridization (FISH), comparative genomes hybridization (CGH) and its further improvement that is array-CGH, and other aspects of microarray DNA technology. The second part deals with the main findings concerning participation of oncogenes and tumor suppressor genes in development and progression of tobacco smoke-associated head and neck cancers.

A role of tobacco products in cancer incidence is commonly known and accepted. It is estimated that roughly 1/3 of all the cancers is resulted from previous exposure to tobacco. An impact of tobacco smoke carcinogens in formation of DNA lesions and mutations is well established. Contrary to that, less is known about rearrangements of chromosomes. Nevertheless, there are many indications associating rearrangements of chromosome arms 3p, 3q, 8q, 9p, 17p i 18q with a clastogenic activity of tobacco smoke. An evolution of cytogenetics from conventional techniques to molecular cytogenetics provides an opportunity to find some links between chromosome aberrations and activation of oncogenes as well as deactivation of tumor suppressor genes.

A review presents an incidence of multiple (second) primary tumors of head and neck region resulted from an exposure to tobacco smoke and ethanol. Further, epidemiology, clinical implications, molecular alterations and an impact of genetic factor are described. Finally, alternative theories of origin of multiple primary tumors are discussed.

The incidence of laryngeal cancer is strongly connected with exposure to tobacco smoke containing at least 40 genotoxic carcinogens. DNA lesions induced by tobacco smoke carcinogens can be turned into stable mutations. Oncogenes and tumor suppressor genes are first of all responsible for initiation of carcinogenesis. The same time cells provide such self-protection processes as: carcinogen detoxication, DNA repair and apoptosis. The initiation of carcinogenesis followed by oncogenesis results from the competition between DNA lesions/mutations formation and the protection processes; the latter are genetically controlled.