Krzysztof Szyfter - Academia.edu (original) (raw)

Papers by Krzysztof Szyfter

Research paper thumbnail of Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss

Biochemical and Biophysical Research Communications, 2010

Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglyco... more Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycosideinduced hearing loss associated mutations.

Research paper thumbnail of Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

The American journal of case reports, 2014

Female, 6 FINAL DIAGNOSIS: Phenotype-genotype discordance in congenital malformations with commun... more Female, 6 FINAL DIAGNOSIS: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: - - Clinical Procedure: - Specialty: Otolaryngology. Congenital defects. Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). Sometimes phenotype may delusively correspond to the characteristic features of a given syndrome, but genotype tests do not confirm its presence. We present the case of a 6-year-old girl admitted to the Clinic of Phoniatrics and Audiology for the assessment of communication in the course of congenital malformations with phenotype characteristic for trisomy 18 (Edwards syndrome). Immediately upon birth, dysmorphic changes suggesting trisomy 18 (Edwards syndrome) were observed, but trisomy 18 was excluded aft...

Research paper thumbnail of SDF1-3' a gene polymorphism is associated with laryngeal cancer

Pathology oncology research : POR, 2010

The SDF1-3' G801A (rs 1801157) polymorphism is associated with increased risk of various type... more The SDF1-3' G801A (rs 1801157) polymorphism is associated with increased risk of various types of cancers, including those of the neck and head. Using PCR-RFLPs, we investigated the distribution of SDF1-3' G801A genotypes in patients with laryngeal cancer (n = 118) and controls (n = 250) in Poland. We found that patients with SDF1-3' A/A and G/A genotypes exhibit a 1.863-fold increased risk of laryngeal cancer (95% CI = 1.177-2.949, p = 0.0086). However, there was no significant increase in risk for the homozygous SDF1-3' A/A genotype OR = 3.235 (95% CI = 0.5330-19.633, p = 0.3329). We also did not observe a significant association between tumor characteristics and prevalence of alleles or genotypes for the SDF1-3' G801A polymorphism. Our findings suggest that the SDF1-3'A variant may be associated with an increased risk of laryngeal cancer.

Research paper thumbnail of The influence of environmental exposure to complex mixtures including PAHs and lead on genotoxic effects in children living in Upper Silesia, Poland

Mutagenesis, 2006

Environmental exposure is a complex mixture of hazardous compounds with different mechanisms of t... more Environmental exposure is a complex mixture of hazardous compounds with different mechanisms of toxicity. In case of concomitant exposure to carcinogenic substances--such as polycyclic aromatic hydrocarbons (PAHs)--and to heavy metals--such as lead (Pb)--the level of DNA damage may be enhanced. Children are considered more vulnerable than adults to chemical toxicants because they take in more toxicants as a proportion of body mass and because of inherent biological growth and developmental factors. The objective of the study was to measure cytogenetic effects in Silesian children and to investigate their relation with the environmental exposure to PAHs and Pb. The examined population included 74 children 5-14-year-old who lived in two cities located in the most polluted centre of the Silesia province. Individual exposure to lead was assessed for each child by measuring lead in blood (PbB), and to PAH by measuring 1-hydroxypyrene in urine (1-OHP), urinary mutagenicity and DNA adducts...

Research paper thumbnail of Analiza kliniczna i histopatologiczna raków płaskonabłonkowych głowy i szyi u młodych dorosłych

Research paper thumbnail of 32P-Postlabelling analysis of DNA adducts in humans: adduct distribution and method improvement

32p-Postlabelling was applied to study the distribution of adducts in white blood cells of foundr... more 32p-Postlabelling was applied to study the distribution of adducts in white blood cells of foundry workers exposed to polycylic aromatic hydrocarbons. The distribution of the adducts among 63 workers followed an apparently trimodal pattern, which could relate to polymorphism in PAH metabolism. A modified postlabelling method is described and some parameters were tested for optimal labelling. The total volume of the polynucleotide kinase reaction is 2/zl, which decreases exposure to radioactivity and costs of isotopes.

Research paper thumbnail of Analysis of chromosome aberrations in cell lines derived from laryngeal cancer in relation to tumor progression

Cell lines provide a good model for studies on molecular and cellular events accompanying neoplas... more Cell lines provide a good model for studies on molecular and cellular events accompanying neoplastic transformation and cancer progression. The data in recent literature suggest an occurrence of repetitive chromosome aberrations that can be linked with particular stages of cancer. Ten cell lines derived from squamous cell carcinoma of the larynx at the University of Turku were karyotyped. The studied cell lines represented a variety of primary locations of the tumors, TNM staging and histological grading. Karyotyping was done by the classical cytogenetic technique with the application of GTG, QFQ and other banding techniques; some complex aberrations were analyzed by the FISH technique. The results document several numerical and structural aberrations. Attention was focused on the monosomy of chromosomes 13, 17 and 18, frequent deletions of the Y chromosome. Structural aberrations were frequently seen at chromosomes 1, 3, 4, 7, 8, 9 and 11, mostly as deletions (usually deletions of a whole arm), translocations, isochromosomes, duplications and marker chromosomes. The study is in progress and aims to find a correlation between particular aberrations and disease staging. At present, two observations seem to be firm: the amplification of the 11q13 region appeared in tumors with a short survival. However, the primary location of the tumor should be taken into account when considering 11q13 as a prognostic marker. The same is applicable for del(9p), which indicates an early stage of disease. Besides the frequent chromosome aberrations, attention should be paid to marker chromosomes that are potentially specific for laryngeal cancer.

Research paper thumbnail of Biological Monitoring of Exposure to Polycyclic Aromatic Hydrocarbon in an Electrode Paste Plant

Journal of Occupational and Environmental Medicine, 1994

In this paper we evaluated the possibility to assess occupational exposure to polycyclic aromatic... more In this paper we evaluated the possibility to assess occupational exposure to polycyclic aromatic hydrocarbons (PAHs) measuring unmetabolized PAHs in urine. With this aim, 24 road paving (RP) workers, exposed to bitumen fumes, and 6 road construction workers (CW), exposed to diesel exhausts, were investigated. Median personal exposure to low boiling PAHs (from naphthalene to pyrene) during the work shift ranged from 0.5 to 369 ng/m 3 , with naphthalene as the most abundant compound. Three urine samples were collected for each worker: baseline (after 2 days of vacation), before-and end-shift samples (in the second part of the work week). The following urinary compounds were measured by headspace-solid phase microextraction GC/MS: naphthalene (U-NAP), acenaphthylene (U-ACY), acenaphthene (U-ACE), fluorene (U-FLE), phenanthrene (U-PHE), anthracene (U-ANT), fluoranthene (U-FLU), pyrene (U-PYR). Urinary PAHs were detected in almost all samples. Median levels for U-NAP, U-PHE, U-PYR and U-FLE in end-shift samples were 82, 48, 54 and 21 ng/L in RP and 69, 14, 24 and 15 ng/L in CW, respectively. Significant differences in the levels of U-PHE, U-FLU and U-PYR were found between RP and CW (p < 0.05). Moreover in RP samples the urinary excretion of most analytes increased during the work shift (p < 0.05). These results suggest that urinary PAHs may be useful biomarkers of occupational exposure. (L. Campo).

Research paper thumbnail of The exposure to PAH of children living in Silesia Province in relation to the polymorphism of detoxification genes

Research paper thumbnail of In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues

Mutation Research-genetic Toxicology and Environmental Mutagenesis, 1999

Malathion [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorodithioate] is a commonly used organoph... more Malathion [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorodithioate] is a commonly used organophosphorus insecticide reported to be genotoxic both in vivo and in vitro, but the reports are conflicting. In order to elucidate the genotoxic potency of the main compounds present in commercial preparations of malathion, the DNA-damaging effect of this insecticide, its major metabolite malaoxon [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorothiolate] and its isomer isomalathion [S-(1,2-dicarboethoxyethyl)O,S-dimethyl phosphorodithioate], all

Research paper thumbnail of Analiza uwarunkowań genetycznych wrodzonej naczyniakowatości krwotocznej choroby Rendu-Oslera-Webera – doniesienia wstępne

Journal of Electrocardiology, 2008

Hereditary haemorrhagic telangiectasia (HHT) known also as Rendu-Osler-Weber syndrome is an autos... more Hereditary haemorrhagic telangiectasia (HHT) known also as Rendu-Osler-Weber syndrome is an autosomal dominant disorder characterized by localized angiodysplasia due to mutations in ENG (endoglin, 9q34.1) or ALK-1 gene (the activin receptor-like kinase 1, 12q13). ENG and ALK-1 are found associated with two disease subtypes designated as HHT1 and HHT2, respectively. Subtype HHT1 remains in the frame of interest of laryngology because of frequent bleeding in head and neck region. The study was designed to identify a genetic background in a large family (29 individuals) with diagnosed HHT. Pedigree analysis showed autosomal dominant pattern of inheritance. Study design comprised segregation analysis to determine locus with subsequent direct sequencing of the gene. Four microsatelite markers (d9s61, d9s65, d12s368, d12s347) with high frequency of heterozygosity in population study were used. The results concerning heterozygosity ranged from 15% to 53%. The established differences were not sufficient enough to indicate co-segregation of the studied loci. DNA sequence analysis in exon 11 of ENG gene did not reveal mutations. The latter result could be explained by an occurrence of mutations in other exons of ENG. The study requires continuation for gene identification and precise genotype-phenotype correlation aiming for an improvement of HHT1 therapy.

Research paper thumbnail of Oxidative DNA Base Modifications and Polycyclic Aromatic Hydrocarbon DNA Adducts in Squamous Cell Carcinoma of Larynx

Free Radical Research, 2003

Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tr... more Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tract, represents an abundant source of reactive oxygen species (ROS), which are believed to play a significant role in mutagenesis and carcinogenesis. An additional source of ROS in tissues exposed to tobacco smoke may be metabolic oxidation of polycyclic aromatic hydrocarbons (PAH). To investigate the relationships between oxidative DNA lesions and aromatic DNA adducts, six modified DNA bases 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine and the total level of PAH-related DNA adducts were measured in cancerous and the surrounding normal larynx tissues (68 subjects), using gas chromatography/isotope-dilution mass spectroscopy with selected ion monitoring and the 32P-postlabeling-HPLC assay, respectively. The levels of oxidative DNA lesions in cancerous and adjacent tissue were comparable; the differences between the two types of tissue were significant only for 5-hydroxypyrimidines (slightly higher levels were observed in the adjacent tissue). Comparable levels of DNA lesions in cancerous and the surrounding normal tissues observed in the larynx tumors support a field cancerization theory. The surrounding tissues may still be recognized as normal by histological criteria. However, molecular alterations resulting from the chronic tobacco smoke exposure, which equally affects larynx epithelia, may lead to multiple premalignant lesions. Thus, a demonstration of similar levels of DNA damage in cancerous and the adjacent tissue could explain a frequent formation of secondary tumors in the larynx and the frequent recurrence in this type of cancer. A weak, but distinct effect of tumor grading and metastatic status was observed in both kinds of tissue in the case of 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine. This effect was displayed as a gradual shift in the data distribution toward high values from G1 through G2-G3 and from non-metastatic to metastatic tumors. Since the levels of oxidative DNA base modifications tended to increase with the tumor aggressiveness, we postulate that the oxidative DNA lesions increase genetic instability and thus contribute to tumor progression in laryngeal cancer. No associations between aromatic adduct levels and oxidative DNA lesions were present, suggesting that the metabolism of PAH does not contribute significantly to the oxidative stress in larynx tissues, remaining the tobacco smoke ROS as a major source of oxidative DNA damage in the exposed tissue.

Research paper thumbnail of CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2005

Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NA... more Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma (SCC) of the larynx. The case-control study was performed in 289 patients with laryngeal SCC and in 316 cancer-free controls; all were Caucasian males from the same region of Poland and current tobacco smokers. The DNA samples were genotyped using PCR-RFLP and multiplex PCR. The variants&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; frequencies in both groups were compared; odds ratios and their 95% confidence intervals were calculated by logistic regression analyses. The CYP1A1*1/*4, CYP2D6*4/*4, NAT2*4/*6A genotypes, as well as the CYP1A1*4, CYP2D6*4 and NAT2*4 alleles, were found at significantly higher frequencies in cases than in controls indicating their role as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk-elevating&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; factors in laryngeal SCC. Combined genotypes, characterized by the presence of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk-elevating&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; variants at more than one locus, often occurred together with the null variant of the GSTM1 gene and homozygous XPD A/A (Lys751Gln, A35931C) genotype. Furthermore, we identified some &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;protective&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; variants, found more frequently in controls than in cases, i.e. the NAT2*6A/*6A and NAT2*5B/*6A genotypes. A distribution of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;protection&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; genotypes/alleles seems to be connected with age as an occurrence or risk genes was more frequent in the group of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;young&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; cases (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 49 years). Accumulation of certain alleles or genotypes of the CYP1A1, NAT2, GSTM1 and XPD seems to be associated with either increased or decreased risk to develop laryngeal SCC. Therefore, polymorphisms in these genes may play a role in the laryngeal cancer etiology.

Research paper thumbnail of Tobacco smoke-induced DNA strand breaks in rat estimated by comet assay

Research paper thumbnail of Cyclin D1 gene ( CCND1 ) polymorphism and the risk of squamous cell carcinoma of the larynx

European Archives of Oto-rhino-laryngology, 2006

Cyclin D1 is one of the key proteins involved in cell cycle control, and it is believed that its ... more 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

Research paper thumbnail of The effect of aryl hydrocarbon receptor ligands on the expression of AhR, AhRR, ARNT, Hif1α, CYP1A1 and NQO1 genes in rat liver

Toxicology Letters, 2006

The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous envi... more The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. AhR together with ARNT, AhRR, HIF1␣ represent a novel basic helix-loop-helix/PAS family of transcriptional regulators. Their interplay may affect the xenobiotic response. In this study, the effect of i.p. administration of different AhR ligands on the expression of AhR, AhRR, ARNT, HIF1␣ and CYP1A1 and NAD(P)H: quinone oxidoreductase (NQO1), the enzymes controlled by AhR were examined in Sprague-Dawley rat liver. Quantitative real-time RT-PCR analysis revealed no changes in the mRNA expression of ARNT and HIF1␣ following 3-methylcholanthrene (3-MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or ␤-naphthoflavone (BNF) treatment. AhRR expression was affected by TCDD but not by BNF and 3-MC. Expression of AhR mRNA and of the markers of its activation, CYP1A1 and NQO1, was significantly increased by administration of TCDD, 3-MC and, to lower extent, BNF.

Research paper thumbnail of Contribution of polymorphism in codon 72 of TP53 gene to laryngeal cancer in Polish patients

Oral Oncology, 2009

The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and bio... more The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and biological activity of this protein, and is associated with several types of cancers. However, the Arg72Pro polymorphism exhibits inconsistent contribution as a risk factor in various cancer types. Therefore, using PCR-RFLPs, we investigated the distribution of Arg72Pro genotypes and alleles in patients with laryngeal cancer (n=123) and controls (n=300) in Poland. We observed that patients with the Pro/Pro and Arg/Pro TP53 genotypes displayed a 1.755-fold increased risk of laryngeal cancer (95% CI=1.149-2.680, P=0.0099). However, we did not find a significant increase in laryngeal cancer risk for the homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530). This result suggests that the TP53Pro variant may contribute to the risk of laryngeal cancer development in Polish patients.

Research paper thumbnail of Molecular and cellular alterations in tobacco smoke-associated larynx cancer

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1999

Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, morta... more Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, mortality from larynx cancer among males has been continuously increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aetiology of laryngeal cancer is strongly associated with exposure to carcinogens present in tobacco smoke. The review describes a sequence of molecular and cellular events from Ž . carcinogenic exposure, DNA adduct formation, detection of mutations in the p53 gene, loss of heterozygosity LOH in chromosomal loci encoding the p53 and p16 genes, and loss of control of the cell cycle. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, and disease progression. The significance of genetic factors as individual risk determinants is discussed in relation to bleomycin-induced chromosome instability and in connection with the occurrence of defects in genes encoding detoxifying enzymes. The question concerning the substantial difference between men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared with female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome. q

Research paper thumbnail of The contribution of the mitochondrial COI/tRNASer(UCN) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients

Molecular Genetics and Metabolism, 2011

Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-ind... more Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed the systematic mutation screening of the COI/tRNA Ser(UCN) genes in 250 unrelated Polish subjects with hearing impairment. Three different homoplasmic sequence variants were identified, including one common polymorphism m.7476 CNT in tRNA Ser(UCN) and two mutations, m.7444 GNA and m.7445 ANG localized in the COI/precursor of tRNA Ser(UCN) . The incidence of m.7444 GNA substitution was estimated at 1.6% (4/250), however variable penetrance of hearing loss, age of onset and hearing thresholds among m.7444 GNA carriers was observed. Two subjects had the positive history of aminoglycoside exposure and one of them harbored both m.7444 GNA and 12S rRNA m.1555 ANG mutations. Those suggest that m.7444 GNA itself is not sufficient to produce a clinical phenotype and additional modifier factors are required for pathogenic manifestation of m.7444 GNA substitution. Moreover, we have described the first Polish family with nonsyndromic hearing loss, harboring m.7445 ANG mutation. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing impairment was included, and 8% when ototoxic effect was excluded. This finding strongly suggests the possible role of m.7445 ANG in susceptibility to aminoglycoside inducedhearing loss.

Research paper thumbnail of Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer

Molecular Biology Reports, 2010

Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. ... more Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. Though, the polymorphic variants of genes encoding enzymes of folate and methionine metabolism may have an effect on DNA methylation. Using PCR-RFLPs, we examined the polymorphism distribution of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR) in patients with larynx cancer (n = 131) and controls (n = 250). Patients with MTR 2756AG or GG genotypes displayed a 1.856 -fold increased risk of larynx cancer (95% CI = 1.1860-2.903, P = 0.0076). However, we did not observe an increased risk for the homozygous GG genotype OR = 1.960 (95% CI = 0.6722-5.713, P = 0.2535). Moreover, we did not observe statistical differences in distribution of MTHFR 677C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T, 1298A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and MTHFD1 1958G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A allele and genotype frequencies in patients and controls. Our findings confirm the significance of the role of the methyl cycle in etiopathogenesis of laryngeal cancer.

Research paper thumbnail of Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss

Biochemical and Biophysical Research Communications, 2010

Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglyco... more Mutations in mitochondrial DNA have been reported as associated with non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed mutational screening of entire 12S rRNA gene in 250 unrelated patients with non-syndromic and aminoglycoside-induced hearing loss. Twenty-one different homoplasmic sequence variants were identified, including eight common polymorphisms, one deafness-associated mutation m.1555 A>G and three putatively pathogenic variants: m.669 T>C, m.827 A>G, m.961 delT+C(n)ins. The incidence of m.1555 A>G was estimated for 3.6% (9/250); however, where aminoglycoside exposure was taken as a risk factor, the frequency was 5.5% (7/128). Substitution m.669 T>C was identified only in patients with hearing impairment and episode of aminoglycoside exposure, which may suggest that such additional risk factors must appear to induce clinical phenotype. Moreover, two 12S rRNA sequence variants: m.988 G>A and m.1453 A>G, localized at conserved sites and affected RNA secondary structure, may be new candidates for non-syndromic and aminoglycosideinduced hearing loss associated mutations.

Research paper thumbnail of Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome)

The American journal of case reports, 2014

Female, 6 FINAL DIAGNOSIS: Phenotype-genotype discordance in congenital malformations with commun... more Female, 6 FINAL DIAGNOSIS: Phenotype-genotype discordance in congenital malformations with communication disorders resembling trisomy 18 (Edwards syndrome) Symptoms: - - Clinical Procedure: - Specialty: Otolaryngology. Congenital defects. Communication process disorders are very frequent in rare cases of chromosomal aberrations (deletions, insertions, and trisomies) such as Down syndrome (trisomy 21), Turner syndrome, Edwards syndrome (trisomy 18), or Patau syndrome (trisomy 13). Sometimes phenotype may delusively correspond to the characteristic features of a given syndrome, but genotype tests do not confirm its presence. We present the case of a 6-year-old girl admitted to the Clinic of Phoniatrics and Audiology for the assessment of communication in the course of congenital malformations with phenotype characteristic for trisomy 18 (Edwards syndrome). Immediately upon birth, dysmorphic changes suggesting trisomy 18 (Edwards syndrome) were observed, but trisomy 18 was excluded aft...

Research paper thumbnail of SDF1-3' a gene polymorphism is associated with laryngeal cancer

Pathology oncology research : POR, 2010

The SDF1-3' G801A (rs 1801157) polymorphism is associated with increased risk of various type... more The SDF1-3' G801A (rs 1801157) polymorphism is associated with increased risk of various types of cancers, including those of the neck and head. Using PCR-RFLPs, we investigated the distribution of SDF1-3' G801A genotypes in patients with laryngeal cancer (n = 118) and controls (n = 250) in Poland. We found that patients with SDF1-3' A/A and G/A genotypes exhibit a 1.863-fold increased risk of laryngeal cancer (95% CI = 1.177-2.949, p = 0.0086). However, there was no significant increase in risk for the homozygous SDF1-3' A/A genotype OR = 3.235 (95% CI = 0.5330-19.633, p = 0.3329). We also did not observe a significant association between tumor characteristics and prevalence of alleles or genotypes for the SDF1-3' G801A polymorphism. Our findings suggest that the SDF1-3'A variant may be associated with an increased risk of laryngeal cancer.

Research paper thumbnail of The influence of environmental exposure to complex mixtures including PAHs and lead on genotoxic effects in children living in Upper Silesia, Poland

Mutagenesis, 2006

Environmental exposure is a complex mixture of hazardous compounds with different mechanisms of t... more Environmental exposure is a complex mixture of hazardous compounds with different mechanisms of toxicity. In case of concomitant exposure to carcinogenic substances--such as polycyclic aromatic hydrocarbons (PAHs)--and to heavy metals--such as lead (Pb)--the level of DNA damage may be enhanced. Children are considered more vulnerable than adults to chemical toxicants because they take in more toxicants as a proportion of body mass and because of inherent biological growth and developmental factors. The objective of the study was to measure cytogenetic effects in Silesian children and to investigate their relation with the environmental exposure to PAHs and Pb. The examined population included 74 children 5-14-year-old who lived in two cities located in the most polluted centre of the Silesia province. Individual exposure to lead was assessed for each child by measuring lead in blood (PbB), and to PAH by measuring 1-hydroxypyrene in urine (1-OHP), urinary mutagenicity and DNA adducts...

Research paper thumbnail of Analiza kliniczna i histopatologiczna raków płaskonabłonkowych głowy i szyi u młodych dorosłych

Research paper thumbnail of 32P-Postlabelling analysis of DNA adducts in humans: adduct distribution and method improvement

32p-Postlabelling was applied to study the distribution of adducts in white blood cells of foundr... more 32p-Postlabelling was applied to study the distribution of adducts in white blood cells of foundry workers exposed to polycylic aromatic hydrocarbons. The distribution of the adducts among 63 workers followed an apparently trimodal pattern, which could relate to polymorphism in PAH metabolism. A modified postlabelling method is described and some parameters were tested for optimal labelling. The total volume of the polynucleotide kinase reaction is 2/zl, which decreases exposure to radioactivity and costs of isotopes.

Research paper thumbnail of Analysis of chromosome aberrations in cell lines derived from laryngeal cancer in relation to tumor progression

Cell lines provide a good model for studies on molecular and cellular events accompanying neoplas... more Cell lines provide a good model for studies on molecular and cellular events accompanying neoplastic transformation and cancer progression. The data in recent literature suggest an occurrence of repetitive chromosome aberrations that can be linked with particular stages of cancer. Ten cell lines derived from squamous cell carcinoma of the larynx at the University of Turku were karyotyped. The studied cell lines represented a variety of primary locations of the tumors, TNM staging and histological grading. Karyotyping was done by the classical cytogenetic technique with the application of GTG, QFQ and other banding techniques; some complex aberrations were analyzed by the FISH technique. The results document several numerical and structural aberrations. Attention was focused on the monosomy of chromosomes 13, 17 and 18, frequent deletions of the Y chromosome. Structural aberrations were frequently seen at chromosomes 1, 3, 4, 7, 8, 9 and 11, mostly as deletions (usually deletions of a whole arm), translocations, isochromosomes, duplications and marker chromosomes. The study is in progress and aims to find a correlation between particular aberrations and disease staging. At present, two observations seem to be firm: the amplification of the 11q13 region appeared in tumors with a short survival. However, the primary location of the tumor should be taken into account when considering 11q13 as a prognostic marker. The same is applicable for del(9p), which indicates an early stage of disease. Besides the frequent chromosome aberrations, attention should be paid to marker chromosomes that are potentially specific for laryngeal cancer.

Research paper thumbnail of Biological Monitoring of Exposure to Polycyclic Aromatic Hydrocarbon in an Electrode Paste Plant

Journal of Occupational and Environmental Medicine, 1994

In this paper we evaluated the possibility to assess occupational exposure to polycyclic aromatic... more In this paper we evaluated the possibility to assess occupational exposure to polycyclic aromatic hydrocarbons (PAHs) measuring unmetabolized PAHs in urine. With this aim, 24 road paving (RP) workers, exposed to bitumen fumes, and 6 road construction workers (CW), exposed to diesel exhausts, were investigated. Median personal exposure to low boiling PAHs (from naphthalene to pyrene) during the work shift ranged from 0.5 to 369 ng/m 3 , with naphthalene as the most abundant compound. Three urine samples were collected for each worker: baseline (after 2 days of vacation), before-and end-shift samples (in the second part of the work week). The following urinary compounds were measured by headspace-solid phase microextraction GC/MS: naphthalene (U-NAP), acenaphthylene (U-ACY), acenaphthene (U-ACE), fluorene (U-FLE), phenanthrene (U-PHE), anthracene (U-ANT), fluoranthene (U-FLU), pyrene (U-PYR). Urinary PAHs were detected in almost all samples. Median levels for U-NAP, U-PHE, U-PYR and U-FLE in end-shift samples were 82, 48, 54 and 21 ng/L in RP and 69, 14, 24 and 15 ng/L in CW, respectively. Significant differences in the levels of U-PHE, U-FLU and U-PYR were found between RP and CW (p < 0.05). Moreover in RP samples the urinary excretion of most analytes increased during the work shift (p < 0.05). These results suggest that urinary PAHs may be useful biomarkers of occupational exposure. (L. Campo).

Research paper thumbnail of The exposure to PAH of children living in Silesia Province in relation to the polymorphism of detoxification genes

Research paper thumbnail of In vitro studies on the genotoxicity of the organophosphorus insecticide malathion and its two analogues

Mutation Research-genetic Toxicology and Environmental Mutagenesis, 1999

Malathion [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorodithioate] is a commonly used organoph... more Malathion [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorodithioate] is a commonly used organophosphorus insecticide reported to be genotoxic both in vivo and in vitro, but the reports are conflicting. In order to elucidate the genotoxic potency of the main compounds present in commercial preparations of malathion, the DNA-damaging effect of this insecticide, its major metabolite malaoxon [S-(1,2-dicarboethoxyethyl)O,O-dimethyl phosphorothiolate] and its isomer isomalathion [S-(1,2-dicarboethoxyethyl)O,S-dimethyl phosphorodithioate], all

Research paper thumbnail of Analiza uwarunkowań genetycznych wrodzonej naczyniakowatości krwotocznej choroby Rendu-Oslera-Webera – doniesienia wstępne

Journal of Electrocardiology, 2008

Hereditary haemorrhagic telangiectasia (HHT) known also as Rendu-Osler-Weber syndrome is an autos... more Hereditary haemorrhagic telangiectasia (HHT) known also as Rendu-Osler-Weber syndrome is an autosomal dominant disorder characterized by localized angiodysplasia due to mutations in ENG (endoglin, 9q34.1) or ALK-1 gene (the activin receptor-like kinase 1, 12q13). ENG and ALK-1 are found associated with two disease subtypes designated as HHT1 and HHT2, respectively. Subtype HHT1 remains in the frame of interest of laryngology because of frequent bleeding in head and neck region. The study was designed to identify a genetic background in a large family (29 individuals) with diagnosed HHT. Pedigree analysis showed autosomal dominant pattern of inheritance. Study design comprised segregation analysis to determine locus with subsequent direct sequencing of the gene. Four microsatelite markers (d9s61, d9s65, d12s368, d12s347) with high frequency of heterozygosity in population study were used. The results concerning heterozygosity ranged from 15% to 53%. The established differences were not sufficient enough to indicate co-segregation of the studied loci. DNA sequence analysis in exon 11 of ENG gene did not reveal mutations. The latter result could be explained by an occurrence of mutations in other exons of ENG. The study requires continuation for gene identification and precise genotype-phenotype correlation aiming for an improvement of HHT1 therapy.

Research paper thumbnail of Oxidative DNA Base Modifications and Polycyclic Aromatic Hydrocarbon DNA Adducts in Squamous Cell Carcinoma of Larynx

Free Radical Research, 2003

Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tr... more Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tract, represents an abundant source of reactive oxygen species (ROS), which are believed to play a significant role in mutagenesis and carcinogenesis. An additional source of ROS in tissues exposed to tobacco smoke may be metabolic oxidation of polycyclic aromatic hydrocarbons (PAH). To investigate the relationships between oxidative DNA lesions and aromatic DNA adducts, six modified DNA bases 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine and the total level of PAH-related DNA adducts were measured in cancerous and the surrounding normal larynx tissues (68 subjects), using gas chromatography/isotope-dilution mass spectroscopy with selected ion monitoring and the 32P-postlabeling-HPLC assay, respectively. The levels of oxidative DNA lesions in cancerous and adjacent tissue were comparable; the differences between the two types of tissue were significant only for 5-hydroxypyrimidines (slightly higher levels were observed in the adjacent tissue). Comparable levels of DNA lesions in cancerous and the surrounding normal tissues observed in the larynx tumors support a field cancerization theory. The surrounding tissues may still be recognized as normal by histological criteria. However, molecular alterations resulting from the chronic tobacco smoke exposure, which equally affects larynx epithelia, may lead to multiple premalignant lesions. Thus, a demonstration of similar levels of DNA damage in cancerous and the adjacent tissue could explain a frequent formation of secondary tumors in the larynx and the frequent recurrence in this type of cancer. A weak, but distinct effect of tumor grading and metastatic status was observed in both kinds of tissue in the case of 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine. This effect was displayed as a gradual shift in the data distribution toward high values from G1 through G2-G3 and from non-metastatic to metastatic tumors. Since the levels of oxidative DNA base modifications tended to increase with the tumor aggressiveness, we postulate that the oxidative DNA lesions increase genetic instability and thus contribute to tumor progression in laryngeal cancer. No associations between aromatic adduct levels and oxidative DNA lesions were present, suggesting that the metabolism of PAH does not contribute significantly to the oxidative stress in larynx tissues, remaining the tobacco smoke ROS as a major source of oxidative DNA damage in the exposed tissue.

Research paper thumbnail of CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2005

Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NA... more Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma (SCC) of the larynx. The case-control study was performed in 289 patients with laryngeal SCC and in 316 cancer-free controls; all were Caucasian males from the same region of Poland and current tobacco smokers. The DNA samples were genotyped using PCR-RFLP and multiplex PCR. The variants&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; frequencies in both groups were compared; odds ratios and their 95% confidence intervals were calculated by logistic regression analyses. The CYP1A1*1/*4, CYP2D6*4/*4, NAT2*4/*6A genotypes, as well as the CYP1A1*4, CYP2D6*4 and NAT2*4 alleles, were found at significantly higher frequencies in cases than in controls indicating their role as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk-elevating&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; factors in laryngeal SCC. Combined genotypes, characterized by the presence of the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk-elevating&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; variants at more than one locus, often occurred together with the null variant of the GSTM1 gene and homozygous XPD A/A (Lys751Gln, A35931C) genotype. Furthermore, we identified some &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;protective&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; variants, found more frequently in controls than in cases, i.e. the NAT2*6A/*6A and NAT2*5B/*6A genotypes. A distribution of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;risk&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;protection&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; genotypes/alleles seems to be connected with age as an occurrence or risk genes was more frequent in the group of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;young&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; cases (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or = 49 years). Accumulation of certain alleles or genotypes of the CYP1A1, NAT2, GSTM1 and XPD seems to be associated with either increased or decreased risk to develop laryngeal SCC. Therefore, polymorphisms in these genes may play a role in the laryngeal cancer etiology.

Research paper thumbnail of Tobacco smoke-induced DNA strand breaks in rat estimated by comet assay

Research paper thumbnail of Cyclin D1 gene ( CCND1 ) polymorphism and the risk of squamous cell carcinoma of the larynx

European Archives of Oto-rhino-laryngology, 2006

Cyclin D1 is one of the key proteins involved in cell cycle control, and it is believed that its ... more 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

Research paper thumbnail of The effect of aryl hydrocarbon receptor ligands on the expression of AhR, AhRR, ARNT, Hif1α, CYP1A1 and NQO1 genes in rat liver

Toxicology Letters, 2006

The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous envi... more The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. AhR together with ARNT, AhRR, HIF1␣ represent a novel basic helix-loop-helix/PAS family of transcriptional regulators. Their interplay may affect the xenobiotic response. In this study, the effect of i.p. administration of different AhR ligands on the expression of AhR, AhRR, ARNT, HIF1␣ and CYP1A1 and NAD(P)H: quinone oxidoreductase (NQO1), the enzymes controlled by AhR were examined in Sprague-Dawley rat liver. Quantitative real-time RT-PCR analysis revealed no changes in the mRNA expression of ARNT and HIF1␣ following 3-methylcholanthrene (3-MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or ␤-naphthoflavone (BNF) treatment. AhRR expression was affected by TCDD but not by BNF and 3-MC. Expression of AhR mRNA and of the markers of its activation, CYP1A1 and NQO1, was significantly increased by administration of TCDD, 3-MC and, to lower extent, BNF.

Research paper thumbnail of Contribution of polymorphism in codon 72 of TP53 gene to laryngeal cancer in Polish patients

Oral Oncology, 2009

The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and bio... more The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and biological activity of this protein, and is associated with several types of cancers. However, the Arg72Pro polymorphism exhibits inconsistent contribution as a risk factor in various cancer types. Therefore, using PCR-RFLPs, we investigated the distribution of Arg72Pro genotypes and alleles in patients with laryngeal cancer (n=123) and controls (n=300) in Poland. We observed that patients with the Pro/Pro and Arg/Pro TP53 genotypes displayed a 1.755-fold increased risk of laryngeal cancer (95% CI=1.149-2.680, P=0.0099). However, we did not find a significant increase in laryngeal cancer risk for the homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530). This result suggests that the TP53Pro variant may contribute to the risk of laryngeal cancer development in Polish patients.

Research paper thumbnail of Molecular and cellular alterations in tobacco smoke-associated larynx cancer

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 1999

Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, morta... more Tumours of head and neck belong to the most frequent types of cancer world-wide. In Poland, mortality from larynx cancer among males has been continuously increasing during the last decades up to 8.4 deaths per 100,000 men in 1993, which exceeds epidemiological records from other countries. The aetiology of laryngeal cancer is strongly associated with exposure to carcinogens present in tobacco smoke. The review describes a sequence of molecular and cellular events from Ž . carcinogenic exposure, DNA adduct formation, detection of mutations in the p53 gene, loss of heterozygosity LOH in chromosomal loci encoding the p53 and p16 genes, and loss of control of the cell cycle. The section concerning DNA adducts includes a discussion of the role of such confounders as exogenous exposure, the age and sex of the subject, and disease progression. The significance of genetic factors as individual risk determinants is discussed in relation to bleomycin-induced chromosome instability and in connection with the occurrence of defects in genes encoding detoxifying enzymes. The question concerning the substantial difference between men and women in larynx cancer morbidity and mortality remains open, even when the significantly higher adduct formation in male DNA compared with female material was taken into account. Preliminary experiments suggest a role of the frequently observed loss of the Y-chromosome. q

Research paper thumbnail of The contribution of the mitochondrial COI/tRNASer(UCN) gene mutations to non-syndromic and aminoglycoside-induced hearing loss in Polish patients

Molecular Genetics and Metabolism, 2011

Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-ind... more Mutations in mitochondrial DNA have been implicated in both, non-syndromic and aminoglycoside-induced hearing loss. In the present study, we have performed the systematic mutation screening of the COI/tRNA Ser(UCN) genes in 250 unrelated Polish subjects with hearing impairment. Three different homoplasmic sequence variants were identified, including one common polymorphism m.7476 CNT in tRNA Ser(UCN) and two mutations, m.7444 GNA and m.7445 ANG localized in the COI/precursor of tRNA Ser(UCN) . The incidence of m.7444 GNA substitution was estimated at 1.6% (4/250), however variable penetrance of hearing loss, age of onset and hearing thresholds among m.7444 GNA carriers was observed. Two subjects had the positive history of aminoglycoside exposure and one of them harbored both m.7444 GNA and 12S rRNA m.1555 ANG mutations. Those suggest that m.7444 GNA itself is not sufficient to produce a clinical phenotype and additional modifier factors are required for pathogenic manifestation of m.7444 GNA substitution. Moreover, we have described the first Polish family with nonsyndromic hearing loss, harboring m.7445 ANG mutation. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing impairment was included, and 8% when ototoxic effect was excluded. This finding strongly suggests the possible role of m.7445 ANG in susceptibility to aminoglycoside inducedhearing loss.

Research paper thumbnail of Polymorphic variants of folate metabolism genes and the risk of laryngeal cancer

Molecular Biology Reports, 2010

Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. ... more Carcinogenesis may result from abnormal methylation of cancer-related genes regulatory sequence. Though, the polymorphic variants of genes encoding enzymes of folate and methionine metabolism may have an effect on DNA methylation. Using PCR-RFLPs, we examined the polymorphism distribution of genes encoding methionine synthase (MTR); 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1); and methylenetetrahydrofolate reductase (MTHFR) in patients with larynx cancer (n = 131) and controls (n = 250). Patients with MTR 2756AG or GG genotypes displayed a 1.856 -fold increased risk of larynx cancer (95% CI = 1.1860-2.903, P = 0.0076). However, we did not observe an increased risk for the homozygous GG genotype OR = 1.960 (95% CI = 0.6722-5.713, P = 0.2535). Moreover, we did not observe statistical differences in distribution of MTHFR 677C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T, 1298A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C and MTHFD1 1958G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;A allele and genotype frequencies in patients and controls. Our findings confirm the significance of the role of the methyl cycle in etiopathogenesis of laryngeal cancer.