INTRODUCTION:Based on recent studies in humans, chemerin has been classified as an adipokine that might be associated with osteoporosis and BMD. Bone loss is common in adolescents with anorexia nervosa (AN). Moreover, dysfunction in the production of chemerin has also been shown. Therefore, we carried out a comparative analysis between chemerin, bone metabolism, the RANKL/RANK/OPG system, and BMD in girls with AN.MATERIAL AND METHODS:Plasma chemerin, OC, CTx, OPG, and sRANKL were determined by ELISA in 75 girls with AN aged 12.6-17.8 years. BMD was assessed by DXA and expressed as Z-score according to the lumbar spine (s) and total body (TB) sites. According to the s-BMD- and TB-BMD Z-score, girls with AN were divided into two subgroups with parallel analyses used: normal (Z-score > -2.0) and low (Z-score ≤ -2.0) s-BMD, and normal (Z-score > -2.0) and low (Z-score ≤ -2.0) TB-BMD.RESULTS:Mean OC and the OPG/sRANKL ratio were markedly lower in the low s-BMD subgroup compared to the normal s-BMD subgroup. The s-Z-score values (both low and normal) correlated significantly and positively with the OPG/sRANKL ratio. Only in the low s-BMD subgroup did chemerin correlate significantly and positively with all nutritional indices and the OPG/sRANKL ratio. In the low TB-BMD subgroup the mean OC and the OPG/sRANKL ratio were lower than in the normal TB-BMD subgroup. The TB-Z-score values (both normal and low) correlated significantly and positively with all nutritional indices and the OPG/sRANKL ratio. The low TB-Z-score values correlated significantly and positively also with chemerin. In the low TB-BMD subgroup chemerin correlated significantly and positively with weight and BMI (expressed as absolute values), Cole index, the duration of the disease, and OPG/sRANKL ratio while its correlation with age was negative.CONCLUSIONS:Undernutrition and associated deficit of adipose tissue may result in inadequate chemerin production and skeletal disorders in girls with AN. Chemerin acts as a coordinator of the dynamic balance between bone metabolism and the OPG/RANK/RANKL system and, in turn, may contribute to the loss of bone mass in girls with AN. The cortical bone site seems to be more severely responsive to chemerin actions than the trabecular bone site.

Streszczenie Niejednoznaczne dane dotyczące zarówno terminologii, diagnostyki, jak i leczenia niedoboru testosteronu u mężczyzn, skłoniły autorów do podjęcia próby krytycznej analizy dotychczasowej wiedzy. Aktualne wytyczne zarówno Amerykańskiego jak i Europejskiego Towarzystwa Urologicznego (EAU i AUA) określają terapię testosteronem jako skuteczną i bezpieczną. Jednak wiele doniesień wskazuje na negatywne skutki tej terapii budząc niechęć do jej stosowania przez lekarzy i potencjalnych pacjentów, głównie w obawie przed rozwojem u tych chorych raka gruczołu krokowego i incydentów sercowo-naczyniowych. Najwięcej wątpliwości zaobserwowano po opublikowaniu w 2013 i 2014 r. dwóch badań retrospektywnych, skutkiem czego było przerwanie terapii u wielu pacjentów, u których obserwowano korzystne działanie terapii testosteronem. Ponadto, u wielu mężczyzn ze wskazaniami do leczenia testosteronem, terapii tej nie zastosowano, w obawie o ich bezpieczeństwo. Najnowsze dane obaw tych jednak nie potwierdzają. W ponad 100 opublikowanych niedawno pracach naukowo-badawczych wykazano korzystny wpływ terapii testosteronem. Amerykańskie Towarzystwo Endokrynologów Klinicznych (AACE) i Amerykańskie Kolegium Endokrynologii (ACE) opracowały wspólnie własną ocenę piśmiennictwa stwierdzając, że nie ma przekonujących dowodów na to, że terapia testosteronem zwiększa ryzyko incydentów sercowo-naczyniowych. Tożsame wnioski płyną z aktualnych wytycznych EAU i AUA.

Aim The gene encoding the vitamin D receptor (VDR) is considered in many studies to be a good candidate responsible for susceptibility to several diseases such as coronary artery disease (CAD). Epidemiological data show that cardiovascular disease is one of the major health problems in Polish society. Basic studies show that genetic factors play a significant role in the pathogenesis of CAD. We conducted this clinical study to determine if the VDR gene polymorphisms TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) could predispose healthy individuals to an increased risk of premature CAD (P-CAD) incidents. Methods We genotyped 845 subjects in a cohort consisting of 386 healthy volunteers with a documented P-CAD incident in their first-degree relatives and 459 healthy volunteers without family history (FH) of P-CAD. TaqI, ApaI, and FokI polymorphisms in VDR were genotyped using TaqMan assays and the endpoint genotyping method (qPCR). Statistical analyses were performed using the Power Analysis Software STATISTICA v.13.3. Results Although no statistical significance was found for TaqI and ApaI genotype frequencies, the AA genotype of FokI polymorphism was significantly more frequent in the study group compared to the control group (24.61% vs. 16.99%). The results of logistic regression analysis suggested a significant association between FokI polymorphism and FH of P-CAD in heathy people under the recessive model (OR: 1.26 (1.07-1.49, p = 0.007)); however, the frequency of VDR haplotypes did not differ significantly between the control and study populations. Conclusions FokI polymorphism is may be associated with FH of P-CAD. FokI polymorphism may predispose to the development of P-CAD among healthy people over the next years.

Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) are subgroups of head and neck squamous cell carcinoma. E2F Transcription Factor 2 (E2F2) could contribute to cancer development, because it plays a critical role in many cellular processes, including the cell cycle, proliferation, differentiation, DNA damage response, and cell death. In the current study, we assessed the associations of five E2F2 polymorphisms (rs6667575, rs3218121, rs3218211, rs3218148, and rs3218203) with OSCC and OPSCC and influence on the TNM staging and grading. This is the first such survey to concern the European population. The study included 94 primary tumour samples following surgical resection from patients, whereas the control group consisted of 99 healthy individuals. We tried a matching of cases and controls for age and sample size. DNA samples were genotyped by employing the 5′ nuclease assay for allelic discrimination. Our results suggested that the most significant difference between the control group and the cancer group was the A/G heterozygote for rs3218121. Samples containing this genotype were mostly found in the control group. In our samples, rs6667575, rs3218121, rs3218211, and rs3218148 polymorphisms may affect the course of OSCC and OPSCC, while rs3218203 was not associated with OSCC and OPSCC. However, further studies are warranted to confirm our findings.

Introduction: Inflammation is supposed to be one of the factors contributing to decreased bone mineral density (BMD) in anorexia nervosa (AN). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple and cost-effective inflammatory markers, well documented as indicators of postmenopausal osteoporosis. This study aimed to assess the relationships between these ratios and BMD in girls with AN. Material and methods: The electronic records of 73 girls hospitalized for AN were analysed retrospectively. The age range of the study group was 12.56–17.67 years. BMD was assessed by dual-energy X-ray absorptiometry (DXA) and expressed as Z-scores according to lumbar spine (s-BMD) and total body (TB-BMD) sites. NLR and PLR were calculated according to complete blood count results. Patients were divided into 2 subgroups with parallel analyses — according to the TB-BMD criterion and the s-BMD criterion: normal (Z-score > –2.0, n = 63) and low s-BMD subgroup (Z-score ≤ –2.0, n = 10), and normal (Z-score > –2.0, n = 45) and low TB-BMD subgroup (Z-score ≤ –2.0, n = 28). Results: In the low s-BMD subgroup a tendency to an increase of mean NLR, PLR, and WBC values was observed. Respective BMD Z-score values correlated significantly and negatively with PLR in the low s-BMD (R = –0.892, p < 0.001) and normal TB-BMD (R = –0.451, p = 0.002) subgroups, while with NLR only in the normal TB-BMD subgroup (R = –0.685, p < 0.001). In the low s-BMD subgroup the PLR was shown to be a significant and independent predictor of s-BMD (β = –0.881, p < 0.001). The PLR contributed to 77.6% of the s-BMD Z-score variability (R 2 = 0.776, p < 0.001). In the normal TB-BMD subgroup, the PLR and NLR levels were significant and independent predictors of TB-BMD (β = –0.352, p = 0.004; β = –0.450, p = 0.001; β = –0.339, p = 0.005, respectively) and explained 44.4% of TB-BMD Z-score variability (R 2 = 0.444, p < 0.001). Conclusions: These results indicate that there might be a relationship between bone mass loss and inflammation expressed as NLR and PLR in adolescent girls suffering from AN. These connections seem to be dependent on the examined skeletal area. NLR and PLR, which are common indicators of morbidity and mortality in many malignancies and inflammatory chronic diseases, can also be useful in the evaluation of bone condition in adolescent females with AN. However, there is a need for further investigation in this field.

Background: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). Methods: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (<10 ng/mL) and 43 (48.31%) in the control group with documented optimum levels of 25(OH)D (>30 ng/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000–14878499; Ch11: 14880058–14880883 and Ch11: 14885321–14886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. Results: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G>A) may influence the structure and function of CYP2R1. Conclusions: Variant NC_000011.10: g.14878291G>A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.

Colorectal cancer is the second and third most common cancer in females and males, respectively. The PD-L1/PD-1 immune checkpoint is an important source of immunosuppression in the tumor microenvironment and is associated with IFNγ. Recent studies have revealed that a significant number of tumor suppressive miRNAs can regulate the expression of PD-L1.                The objective quantification of selected microRNAs using the miREIA method in CRC tissue was performed. We investigated the roles of miR-93-5p and miR-142-5p expression and the levels of IFNγ in regulating the expression of PD-L1 in tumor and margin tissues of CRC in relation to the histological grade, TNM classification, and tumor localization. 37 samples of tumor and margin tissues from CRC patients were evaluated. MiR-93-5p and miR-142-5p levels were measured by a method for quantitative measurement of human microRNA (miREIA). The concentrations of PD-L1 and IFNγ were determined by the ELISA kit. We found higher concentrations of miR-93-5p, PD-L1 and IFNγ in tumor samples compared to tumor margin samples. A significant correlation was found between PD-L1 and IFNγ in tumor and margin specimens; between miR-142-5p and miR-93-5p levels  in tumor and margin specimens. A higher level of miR-93-5p was found in tumor margin tissues on the left side of the colon. Patients with distant metastases were characterized by higher miR-93-5p concentration compared to patients without metastases. CRC is an important source of PD-L1, IFNγ and miR-93-5p expression. Understanding the mechanisms underlying intratumoral PD-L1 expression may open new opportunities for targeted immunotherapy for colorectal cancer.

The head and neck squamous cell carcinoma (HNSCC) is an aggressive human malignancy diagnosed in more than 800 000 new cases worldwide, and mostly arises in the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx. The study presented here aimed to determine a possible association of rs11515 and rs3088440 gene polymorphisms in the CDKN2A gene (cyclin dependent kinase inhibitor 2A), as well as rs769412 and rs937283 in the MDM2 gene (murine double minute 2), with oral cavity cancer in a sample of Polish population; CDKN2A is crucial in regulating the cell cycle while MDM2 is an oncogene involved in regulating cell proliferation and apoptosis. The study included 95 primary tumor samples following surgical resection from patients, and the control group consisted of 100 healthy individuals. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays (Applied Biosystems, USA). There was no significant association between any of the polymorphism (rs11515, rs3088440, rs769412 and rs937283) and the oral cavity cancer risk. We found that the AA homozygotes for rs3088440 were significantly more frequent in the control group (OR=0.046, p<0.0001). In addition, the GG genotype of rs769412 was not found in any group. We found no influence of the examined genotypes on clinicopathological parameters, such as T, N and grading values in patients with oral cavity cancer. The results of this study indicate that none of the investigated polymorphisms were associated with the risk of oral cavity cancer in the examined sample of the Polish population.

Cyclooxygenase 1 and 2 (COX-1, COX-2) are enzymes that catalyze the first reaction in the arachidonic acid pathway. COXs are the therapeutic target for non-steroidal anti-inflammatory drugs. Inhibition of COX enzymatic activity has an analgesic, anti-inflammatory and sometimes antiplatelet effect. Single-nucleotide polymorphisms (SNPs) within genes encoding COX-1 and COX-2 (PTGS1, PTGS2) influence the risk of pain and their intensity in some diseases. They also affect the effectiveness of NSAID therapy in rheumatoid diseases. Moreover, the relationship between certain polymorphisms of PTGS2 and a higher risk of migraine and the development of aspirin resistance in the prophylaxis of cardiovascular diseases was demonstrated. The isoform of cytochrome P450, CYP2C9 has a significant influence on the efficacy and safety of NSAID use. It is responsible for the metabolism and speed of removal of these drugs. The occurrence of some of its polymorphic forms is associated with a decrease in CYP2C9 enzymatic activity, leading to changes in the pharmacokinetics and pharmacodynamics of NSAIDs. The prolonged half-life and decrease in clearance of these drugs lead to serious side effects such as hepatotoxicity, nephrotoxicity, anaphylactic reactions, cardiovascular or gastrointestinal incidents. Studies on polymorphisms of cyclooxygenases and CYP2C9 may improve the safety and efficacy of NSAIDs therapy by adjusting the dose to individual polymorphic variants, as well as expanding knowledge about the pathomechanism of inflammatory diseases.

INTRODUCTION:Colorectal cancer (CRC) is the second most common malignant neoplasm in men and third in women. It is also the third leading cause of cancer-related death, killing annually >700,000 patients in the world. The global burden of CRC is expected to increase by 60% to >2.2 million new cases and 1.1 million deaths by 2030. The pathogenesis of cancer mainly depends on angiogenesis. This process plays a key role in the growth and infiltration of tumors which is essential for distant metastases. A large number of biochemical pathways is involved in the regulation of angiogenesis. As a subject of our study, we chose chemerin/chemokine-like receptor 1 (CMKLR1) pathway which is responsible for the angiogenic processes in malignant neoplasms.AIM OF THE STUDY:To assess the CMKLR1 level and the concentrations of the two markers of angiogenesis, matrix metalloproteinase (MMP)-9 and vascular cell adhesion molecule (VCAM)-1, in tumor and margin tissues of CRC in relation to histological grade and TNM classification.MATERIALS AND METHODS:The study used 47 samples of tumor and margin tissues derived from CRC patients. To determine the concentration of CMKLR1, MMP-9, and VCAM-1, we used the commercially available enzyme-linked immunosorbent assay kit.RESULTS:We found a significantly higher concentration of CMKLR1 and MMP-9 in tumor tissue compared to margin. There was no difference in VCAM-1 concentration between tumor and margin. The margin concentration of CMKLR1 was significantly correlated with that of both MMP-9 and VCAM-1. The margin concentration of VCAM-1 was correlated with that of MMP-9. Additionally, we observed that the tumor levels of CMKLR1 and MMP-9 were positively correlated with the tumor size (T parameter).CONCLUSION:CMKLR1 activity may be associated with the angiogenic process in CRC via MMP-9 activity. Further research, involving a larger sample, may verify whether chemerin/CMKLR1 axis could be considered as a suitable target in novel molecular therapies.

Colorectal cancer is a common malign disease of the gastrointestinal tract. The cancer survival rate depends on the stage of the disease at detection time. It is well known that several molecular mechanisms are involved in cancer and some molecules might affect or modulate cancerogenesis. The aim of the study was to assess the levels of sICAM-1, sELAM-1, TNFα and sTNFR1 protein in tumor and corresponding normal mucosa in a group of patients with colorectal adenocarcinoma and also associations of these parameters with demographic and clinical profiles of the patients. Tissue specimens were obtained during resection of neoplastic lesions. Protein levels were assayed in tissue homogenates by ELISA. The protein level of sICAM-1 in tumor was significantly increased in comparison to the corresponding normal mucosa (80.06 ng/mg vs 69.53 ng/mg, p=0.02). Furthermore, a significant positive correlation between sICAM-1 and sTNFR1 proteins levels in tumor (rs=0.58, p<0.001) and in corresponding normal mucosa (rs=0.48, p<0.001) was found. Also, significant correlations in corresponding normal mucosa were found between sELAM-1 and sICAM-1 (rs=0.58, p<0.001) and between sTNFR1 and sELAM-1 (rs=0.57, p<0.001). Significantly higher level of sTNFR1 in corresponding normal mucosa samples of patients with distant metastases was observed (p=0.04). Obtained results suggest that sICAM-1 protein could be considered as colorectal cancer marker. Furthermore, sTNFR1 also has the potential to become a good prognostic marker used during monitoring of the patients. Nevertheless, a further study in this area to confirm this correlation is required.

In recent years, people have had high hopes for the possibility of using measurements of the so-called modern bone turnover markers in diagnosis, diagnostics of the course and the prediction of the occurrence of complications of bone metabolic diseases, especially osteoporosis. So far, several diagnostic markers of bone turnover have been identified, particular importance attached to PINP and CTx. However, many studies have highlighted that their use in the diagnosis of osteoporosis is rather limited due to their inter-individual and intra-individual variability, tissue non-specificity, the inability to evaluate individual bone tissue compartments, and the ability to assess metabolic activity of only osteoblasts and/or osteoclasts without osteocytes. The data presented in the thesis indicates the potential usefulness of sclerostin measurements, primarily associated with metabolic activity of osteocytes, periostin, as the indicator of metabolic activity of periosteum and microRNAs as the group of specific markers in the early detection of osteoporosis. All of the above-mentioned candidates could possibly become a predictor of osteoporotic fractures: sclerostin in patients with type 2 diabetes; periostin, especially in non-vertebral fractures in postmenopausal women and microRNA in early prediction of these fractures. However, many of the studies underline some of the limitations associated with their use in the diagnosis of osteoporosis. Ambiguous results of the presented studies may be primarily due to population selection, population size, type of fractures and duration of the observation itself. An objective judgement will be made when an adequate number of standardized and independent studies will allow for the exclusion or validation of each of them in clinical practice.

The main aim of this work was to collect and present the polymorphisms that have been identified and tested and that may potentially have an influence on the effect of analgesic therapies. Opioid drugs are one of the most commonly used painkillers in the treatment of postoperative, neoplastic and post-traumatic pain. Opioid receptors and their types: μ, δ, κ, purinergic and adrenergic receptors contribute to nociceptive stimulation and their modulation. The analgesic effect induced by opioids is dependent on many factors, such as age, sex, body mass and the occurrence of different polymorphic variants of genes encoding opioid, purinergic and adrenergic receptors. Many polymorphisms have been identified within the following genes: OPRM, OPRK, OPRD, ADRB1 and P2RX7, encoding the following receptors: μ, κ, δ, purinergic P2X and β1-adrenergic. The most common polymorphism is the single nucleotide polymorphism (SNP-single nucleotide polymorphism). The occurrence of some polymorphic forms may generate differences in expression and have an impact on the physicochemical properties of receptors, which results in different levels of analgesia in the population and the generation of side effects. The relation between the occurrence of polymorphic variants of the genes of receptors participating in nociceptive stimulation and the increased or reduced demand for opioids necessary to achieve analgesia has been confirmed. Mechanisms in which polymorphisms affect the modification of the anesthetic response to opioids in most cases remain unknown. Further research on opioid, purinergic and adrenergic receptors polymorphisms may improve the effectiveness of opioid therapies by regulating the dose to the patient’s individual pain phenotype, and may reduce the risk of side effects resulting from using too high doses of the drug.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common human malignancy in the world, with high mortality and poor prognosis for patients. Among the risk factors are tobacco and alcohol intake, human papilloma virus, and also genetic and epigenetic modifications. Many studies show that epigenetic events play an important role in HNSCC development and progression, including DNA methylation, chromatin remodeling, histone posttranslational covalent modifications, and effects of non-coding RNA. Epigenetic modifications may influence silencing of tumor suppressor genes by promoter hypermethylation, regulate transcription by microRNAs and changes in chromatin structure, or induce genome instability through hypomethylation. Moreover, getting to better understand aberrant patterns of methylation may provide biomarkers for early detection and diagnosis, while knowledge about target genes of microRNAs may improve the therapy of HNSCC and extend overall survival. The aim of this review is to present recent studies which demonstrate the role of epigenetic regulation in the development of HNSCC.

Paediatric age is a crucial time for bone mass accrual.Every deterioration of bone status in this period of life can affect the condition of the skeleton in the future.The awareness of primary and secondary disorders affecting bone health is vital for the identification of children at risk of developing osteoporosis.Among currently available methods of measuring bone mineral density in children, dual energy X-ray absorptiometry (DXA) remains the method of choice.However, the interpretation of a paediatric DXA report is complicated, which can lead to a misdiagnosis.Unlike in adults, the result is given in the Z-score; the T-score should not be taken into account.The preferred sites of measurement are the total body less head, and the lumbar spine.The current recommendations for bone mineral density assessment are provided by the International Society for Densitometry.

Purpose. The current study aimed to examine the association between head and neck squamous cell carcinoma (HNSCC) and infection with different human papillomavirus virus (HPV) subtypes, including analysis of promoter methylation of several genes (APC, CDKN2A, MGMT, CDH1 and TIMP3) and the correlation with their mRNA expression in tumours and surgical margins. Methodology. In 47 patients with a primary tumour of the oral cavity, HPV detection and identification of 33 subtypes was performed after previous DNA isolation using a GenoFlow HPV Array Test Kit. Results. Fifteen patients (31.92%) were HPV [+] and the following HPV types were detected: 16 (46.67%), 18 (6.67%) and 43/44 (40%). This study is the first to describe HPV 43/44 subtypes in HNSCC in a Polish population. We noted no clinical significance of HPV [+] HNSCC compared to HPV [−], however, this differed among HPV subtypes. CDKN2A promoter methylation was more frequent in HPV‐16/18 patients compared to HPV43/44 patients, but there was no difference in gene expression level between HPV [+] and [−] patients. Conclusion. We detected HPV infection in 31.92% of oral cancer cases. HPV 16, along with HPV 43/44, were the most frequent subtypes. Knowledge of HPV [+] HNSCC biology may be useful in establishing the prognosis and developing novel therapies in future.

Background: Interleukin 15 (IL-15) plays a key role in the muscle-fat interaction, reducing adipose tissue mass without changes in the lean body mass and reduction of food intake. Here we assess serum IL-15 levels in girls with anorexia nervosa (AN) relative to obese and normal weight female adolescents.Methods: Serum IL-15 concentrations were evaluated using a commercially available ELISA kit in 32 Polish girls with restrictive AN, 29 girls with obesity (O), and 21 healthy controls (C). Anthropometric measurements (weight, height, BMI) and laboratory assays (serum fasting glucose, insulin, HOMA-IR, total cholesterol, HDL, LDL, triglycerides, and C-reactive protein (CRP)) were performed.Results: Mean serum IL-15 in the AN group was significantly higher than in C, but lower than in O. In all examined girls, significant positive correlations between IL-15 and body weight, BMI, insulin, HOMA, LDL, triglycerides and CRP were noted. We also observed an inverse relationship between IL-15 and HDL.Conclusions: Our study demonstrated that serum IL-15 concentrations in adolescent girls with AN and obesity are significantly elevated in comparison to normal weight controls. However, the role of IL-15 in the pathogenesis of AN and obesity remains still unclear.

The head and neck squamous cell carcinoma, which are located in different anatomical structures like: oral cavity, throat and larynx, are becoming a major clinical problem due to the ever increasing number of cases and also due to difficulty with treating patients. Among the risks factors associated with that group of cancers the exogenous factors such as: exposure to carcinogens in tobacco smoke, alcohol abuse, impropriety dietary habits, poor oral hygiene as well as infection with the human papillomavirus and infection with Epstein-Barr virus, are well-known and had been described. The second potential group of the risk factors are endogenous factors such as genetic predisposition and disorder immune system. Recently, in view of technical progress of molecular biology, the aim of researches became the polymorphisms the most of genes encoding proteins with a wide variety of functions. In the present study we comprehensively discussed the problems associated with the molecular basis of development the head and neck squamous-cell carcinoma. More specifically, this study investigated the single nucleotide polymorphisms and mutations of genes involved in cell cycle control (TP53, p73, CDKN1A, CDKN2A, MDM2, E2F1, E2F2 and EGFR) and in different pathways of DNA repair (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, OGG1, XRCC1, NBS1, RAD51, BRCA2, XRCC2, XRCC3, XRCC5 and XRCC6). The results of studies indicate a mixed picture of genetic predisposition of the head and neck cancers. Nevertheless, it can be observed that a single polymorphism of specific gene moderately influence on the pathogenesis of that cancers. Commonly, coexistence of few polymorphism at the same time may increase the cancer risk significantly. It is undeniable that the issues discussed in that article should be the subject of further analysis.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and 242 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using Pearson's χ2 test analysis. Our results indicated that the MGMT rs12917 TT genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A allele were associated with increased HNSCC risk. We noted higher risk of nodal metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic defect are unknown and hence further studies need to be carried out. Our data suggest that the examined polymorphisms may be considered as potential prognostic factors for HNSCC risk and outcome. Further studies are necessary to verify our results.