Jurek Olszewski

Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck

BackgroundThe genes of base excision repair (BER) pathway have been extensively studied in the association with various human cancers. We performed a case-control study to test the association between two common single nucleotide polymorphisms (SNPs) of XRCC1 gene with human head and neck squamous cell carcinoma (HNSCC).MethodsThe genotype analysis of Arg194Trp and Arg399Gln gene polymorphisms for 92 HNSCC patients and 124 controls of cancer free subjects, in Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP) with endonuclease Msp I.ResultsNo altered risk has been found individually for these SNPs, however haplotypes analysis showed high association with head and neck cancer. The highest frequency, according to wild-type of Arg194Arg and Arg399Arg genotypes, was identified for Arg194Trp-Arg399Arg haplotype (OR, 2.96; 95% CI, 1.01–8.80).ConclusionFinally, we identified the combined Arg194Trp-Arg399Arg genotype of base excision repair gene XRCC1 that was associated with HNSCC and may have an impact on identification of a high-risk cancer population.

Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population

Genetic variations in DNA repair genes may affect an individuals susceptibility to head and neck cancer. We performed a case-control study to test the association between head and neck cancer risk and two polymorphisms: the C722T of the XRCC3 and the G135C of the RAD51-genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02-14.74) as well as 722TT (OR 4.65; 95% CI 2.30-9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61-4.16 and OR 5.54; 95% CI 3.22-9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69-9.90) and HNSCC (OR 6.04; 95% CI 3.69-9.90) and the 135GC variant of the RAD51 gene. The gene-gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55-9.75) as well as the 722TT/135GC genotypes (OR 5.33; 95% CI 1.96-14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22-4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69-7.76 for 722TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85-10.28 and 1.82-7.35, respectively) and HNSCC patients (ORs 2.94-13.93 and 1.36-3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44-6.12 and 3.52-8.43, respectively) and HNSCC subjects (ORs 2.71-7.01 and 2.33-4.62, respectively). In conclusion our data showed that the C722T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population.

Polymorphism of the DNA repair genes RAD51 and XRCC2 in smoking- and drinking-related laryngeal cancer in a Polish population.

Introduction Cigarette smoke and alcohol can generate reactive oxygen species, which may induce DNA double-strand breaks (DSBs), the most serious DNA lesion. In humans, DSBs are repaired mainly by non-homologous end joining and homologous recombination repair (HRR). Several polymorphisms in the DNA repair gene have been extensively studied in the association with various human cancers. In the present work we investigated the association between polymorphisms of two HRR genes, XRCC2 and RAD51, and tobacco- and alcohol-related larynx cancer in a Polish population. Material and methods Two polymorphisms of the XRCC2 gene, –41657C > T (rs718282) and 31479G > A (rs3218536), as well as one polymorphism of the RAD51 gene, –135G > C (rs1801320), were investigated by PCR-RFLP in 253 patients with larynx cancer and 253 age- and sex-matched non-cancer controls. Results Analysis of the gene-smoking and -drinking interactions revealed a weak association between larynx cancer and the –41657C > T polymorphisms of the XRCC2 gene among the moderate alcohol drinkers. The C allele of the –135G > C polymorphism of RAD51 increased cancer risk in the smoker group. Increased risk was also found for heavy drinkers. Additionally, there were no significant differences between distributions of genotypes in subgroups assigned to different TNM stages and grades. Conclusions The results indicated that the –135G > C polymorphism of the RAD51 gene may be associated with smoking- and drinking-related larynx cancer in Poland.

The Association between Positional Vertebral and Basilar Artery Flow Lesion and Prevalence of Vertigo in Patients with Cervical Spondylosis

OBJECTIVE: The aim of our investigations was to characterize the relationship between basilar artery (BA) flow velocity in patients with cervical spondylosis and age, grade of radiological changes, prevalence of vertigo, and decreased blood flow velocity through vertebral arteries (VA) after head rotation. STUDY DESIGN AND SETTING: A prospective, controlled study in academic neurotology was conducted. We examined 80 patients with radiological evidence of cervical spondylosis. Forty patients complained of positional vertigo lasting more than 6 months. Patients were examined by transcranial Doppler ultrasound with head rotations. RESULTS: We showed significant association between velocity flow in basilar artery after neck rotation and age, prevalence of vertigo, grade of radiological changes, and positional vertebral artery flow lesion. CONCLUSION: Spondylotic-induced VA compression may be the reason for decreased blood flow velocity in the basilar artery during head rotation, which may be of particular importance for older patients, especially complaining of vertigo. SIGNIFICANCE: Every patient with high-grade cervical spondylosis, especially complaining of vertigo, should be examined by using TCD (transcranial Doppler) with head rotations. In case of positional blood flow reduction during head rotation, further angiographic examination should be undertaken so as to plan suitable treatment.

MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study.

In the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR-restriction fragment lenght polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19–2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07–10.05) variants of the OGG1 gene. The gene–gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25–3.11), (OR 3.54; 95% CI 1.39–9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non-smoking status in HNSCC (OR 0.34; 95% CI 0.17–0.66). We also found a link between gene–gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17–4.20 and 2.18–5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population.

Diagnostyka i leczenie szumów usznych na podstawie własnych doświadczeń

INTRODUCTION The aim of the study was to analise tinnitus diagnosis and treatment on the basis of our experiences. MATERIAL AND METHODS 137 patients hospitalizated in Otolaryngology and Laryngological Oncology Clinic because of tinnitus (88 women - 64% and 49 men - 35,8%) were included to the study. The diagnostic procedures were unified that enabled put forward correct diagnosis. After history and otoscopy, detailed audiologic diagnostic procedures (pure tone audiometry, suprathreshold audiometry, speech audiometry, acoustic immittance measures, auditory brainstem responses) were taken. Electronystagmography and videonystagmography, tinnitus loudness match, head and neck radiologic examinations supplemented diagnostic procedures. Alternative tinnitus treatment options were applied. RESULTS Study confirmed that tinnitus is the most frequent in patients above 50 years old (67,8% of participants). Tinnitus frequently coexist with bilateral sensorineural hearing impairment (69,1% of participants). 40,1% from asalysed group of patients complained of tinnitus of medium frequencies and 30,6% of patients complained of high frequency tinnitus. 42,3% of participants suffered from vertigo. CONCLUSIONS The risk of tinnitus increases in patients above 55 years old that suffer from metabolic conditions and cervical spondylosis. Tinnitus frequently coexist with bilateral sensorineural hearing impairment and are bilateral or they are noticeable in better hearing ear. The most beneficial to tinnitus is causal and symptomatic treatment with several methods application.Summary Introduction The aim of the study was to analyse tinnitus diagnosis and treatment on the basis of our experiences. Material and methods 137 patients hospitalizated in Otolaryngology and Laryngological Oncology Clinic because of tinnitus (88 women – 64% and 49 men – 35,8%) were included to the study. The diagnostic procedures were unified that enabled put forward correct diagnosis. After history and otoscopy, detailed audiologic diagnostic procedures (pure tone audiometry, suprathreshold audiometry, speech audiometry, acoustic immittance measures, auditory brainstem responses) were taken. Electronystagmography and videonystagmography, tinnitus loudness match, head and neck radiologic examinations supplemented diagnostic procedures. Alternative tinnitus treatment options were applied. Results Study confirmed that tinnitus is the most frequent in patients above 50 years old (67,8% of participants). Tinnitus frequently coexist with bilateral sensorineural hearing impairment (69,1% of participants). 40,1% from asalysed group of patients complained of tinnitus of medium frequencies and 30,6% of patients complained of high frequency tinnitus. 42,3% of participants suffered from vertigo. Conclusions The risk of tinnitus increases in patients above 55 years old that suffer from metabolic conditions and cervical spondylosis. Tinnitus frequently coexist with bilateral sensorineural hearing impairment and are bilateral or they are noticeable in better hearing ear. The most beneficial to tinnitus is causal and symptomatic treatment with several methods application.

Zastosowanie testu VHIT (Videonystagmography Head Impulse Test) w diagnostyce uszkodzeń kanałów półkolistych

Summary Introduction The aim of that work was to evaluate the usefulness of VHIT (Videonystagmography Head Impulse Test) in the diagnostics of injuries to the semicircular canals. Material and methods The tests covered 58 patients aged 20–27, including 34 women and 24 men. Any deviations within the vestibular organs was excluded in the interview, otorhinolaryngological examination and full videonystagmographic test. The tests checked functions of the semicircular canals in the following way: in a sitting position and the head leaned forward at 30° the patient was looking at a motionless point while quick movements to the left or right were performed to stimulate a particular lateral semicircular canal. When the vertical semicircular canals were tested the head was inclined laterally to the right side at 45°. Then similar movements were performed forwards (stimulation of the left anterior semicircular canal) and backwards (stimulation of the right posterior semicircular canal). When the head was leaned laterally to the left at 45° the right or left anterior semicircular canal was stimulated respectively. Functions of the canal were determined on the basis of gain (%). Results of the tests In 58 patients the gain value for particular semicircular canals was normal, and the mean values presented as follows: the lateral semicircular canal: 11.9%±10.2, the anterior semicircular canal: 17.5%±11.6 and the posterior semicircular canal: 19.2%±13.5, whereas on the left side: 10.3%±7.9, 18.1%±11.1, 15.1%±12.3 respectively. In one man the gain value for the right posterior semicircular canal was found significantly above the standard value – 71%. Conclusion VHIT showed much more sensitive than a full videonystagmographic test.

Role of impaired DNA repair in genotoxic susceptibility of patients with head and neck cancer.

DNA repair is critical for genotoxic susceptibility and cancer development. Forty-seven patients with head and neck squamous cell carcinoma (HNSCC) and 38 healthy controls were enrolled in this study. Among the patients, 16 subjects had metastasis of HNSCC. The extent of DNA damage, including oxidative lesions, and efficiency of repair after genotoxic treatment with hydrogen peroxide were examined using the alkaline comet assay. HNSCC cells were sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by hydrogen peroxide were repaired less effectively in cancer cells from patients with metastasis than in cells from healthy controls. We suggest that impaired DNA repair might play a role in genotoxic susceptibility of patients with head and neck cancer. Finally, as a consequence of this finding we have shown that treatment with DNA-reactive drugs could be considered as an effective therapy strategy for head and neck cancer.

Association of the −33C/G OSF-2 and the 140A/G LF gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population

Nasal polyps are strongly associated with a risk of chronic rhinosinusitis development as well as other obstruction including asthma and allergy. The following study tested the association of the 140A/G polymorphism of lactoferine (LF) encoding gene and the −33C/G polymorphism of osteoblast-specific factor-2 (OSF-2) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex, age and ethnicity matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls and gene polymorphisms were analyzed by restriction fragments length polymorphism polymerase chain reaction (RFLP-PCR). We reported that the 140A/G LF (OR 4.78; 95% CI 3.07–7.24), the −33C/G OSF-2 OR 3.48; 95% CI 2.19–5.52) and the −33G/G OSF-2 (OR 16.45; 95% CI 6.71–40.30) genotypes were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the −33C/G (OR 3.72; 95% CI 2.24–6.19 and OR 15.11; 95% CI 5.91–38.6) and −33G/G (OR 3.73; 95% CI 2.24–6.19 and OR 14.07; 95% CI 5.47–36.16) genotypes of the OSF-2 as wells as 140A/G (OR 3.89; 95% CI 2.40–6.31 and OR 3.62; 95% CI 2.45–5.34) genotype of OSF-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the −33C/G (OR 2.40; 95% CI 1.23–4.69 and OR 2.40; 95% CI 1.23–4.69, respectively) and −33G/G (OR 16.01; 95% CI 5.77–44.41 and OR 17.90; 95% CI 6.53–49.05, respectively) genotypes of the OSF-2 as wells as 140A/G (OR 3.22; 95% CI 1.74–6.11 and OR 3.25; 95% CI 1.75–6.04, respectively) genotypes with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that LF and OSF-2 gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyps’ formation which may also depend on asthma or allergy. Our results showed that the 140A/G polymorphism of LF gene and the −33C/G polymorphism of the OSF-2 gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.

Impaired nucleotide excision repair pathway as a possible factor in pathogenesis of head and neck cancer.

Tobacco smoking is one of the major risk factors in pathogenesis of head and neck squamous cell carcinomas (HNSCC). Many of the chemical compounds present in tobacco are well-known carcinogens which form adducts with DNA. Cells remove these adducts mainly by the nucleotide excision repair pathway (NER). NER also eliminates a broad spectrum of pyrimidine dimers (CPD) and photo-products (6-4PP) induced by UV-radiation or DNA cross-links after cisplatin anti-cancer treatment. In this study DNA damage and repair was examined in peripheral blood lymphocytes obtained from 20 HNSCC patients and 20 healthy controls as well as HTB-43 larynx and SSC-25 tongue cancer cell lines. DNA repair kinetics in the examined cells after cisplatin or UV-radiation treatment were investigated using alkaline comet assay during 240min of post-treatment incubation. MTT assay was used to analyse cell viability and the Annexin V-FITC kit specific for kinase-3 was employed to determine apoptosis after treating the cells with UV-radiation at dose range from 0.5 to 60J/m(2). NER capability was assessed in vitro with cell extracts by the use of a bacterial plasmid irradiated with UV-light as a substrate for the repair. The results show that lymphocytes from HNSCC patients and HTB-43 or SSC-25 cancer cells were more sensitive to genotoxic treatment with UV-radiation and displayed impaired DNA repair. Also evidenced was a higher rate of apoptosis induction after UV-radiation treatment of lymphocytes from the HNSCC patients and the HTB-43 cancer cells than after treatment of those from healthy donors. Finally, our results showed that there was a significant decrease in NER capacity in HTB-43 or SSC-25 cancer cells as well as in peripheral blood lymphocytes of HNSCC patients compared to controls. In conclusion, we suggest that the impaired NER pathway might be a critical factor in pathogenesis of head and neck cancer.