Alina Morawiec-Sztandera

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.

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.

Association of microRNA-93, 190, 200b and Receptor Status in Core Biopsies from Stage III Breast Cancer Patients

Oncologists now favor more personalized treatment strategies in breast cancer patients. Gene expression analysis has been widely used, but less is known about epigenetic factors, for example, microRNAs (miRNAs). The aim of this study was to determine the relationship between selected miRNAs and receptor status in core biopsies sampled before preoperative chemotherapy in stage III locally advanced breast cancer (LABC) patients. In 37 LABC core biopsies, three miRNAs per sample were analyzed: hsa-miR-93-5p, hsa-miR-190a, and hsa-miR-200b-3p, and hsa-miR-103a-3p as an endogenous control (TaqMan(®) RT-PCR; Applied Biosystems). Receptor status was determined by a dedicated pathologist. The Mann-Whitney U, Shapiro-Wilk, and Levenes tests were used to compare related samples. Levels of miRNA-93 differed significantly in core biopsies of LABC patients with different expressions of ER (estrogen receptor) and PR (progesterone receptor). Higher levels of miRNA-93 were found in ER-negative (p=0.0027) and PR-negative patients (p=0.0185). Levels of miRNA-190 and 200b did not differ significantly in core biopsies of LABC patients who expressed ER and PR differently (p=0.7727, p=0.9434, p=0.6213, and p=0.1717). Levels of miRNA-93, 190, and 200b were not significantly different in core biopsies of LABC patients with different HER2 (human epidermal growth factor 2) expressions (p=0.8013, p=0.2609, and p=0.3222). The assessment of core biopsy miRNA profiles and receptor-based subtypes may identify new signaling pathways for improved breast cancer classification.

Leczenie chirurgiczne guzów nowotworowych ślinianek

INTRODUCTION Tumors of parotid gland represent a diverse group of neoplasms with varied clinical behaviors. MATERIAL AND METHODS The diagnostic methods and treatment of salivary gland tumors are presented in this paper. The authors describe the group of 44 patients with salivary gland tumors treated surgically in ENT Departament Laryngology of Medical University in Łódź. Enucleation, partial and total parotidectomy were performed. Neurosign 100 unit was used during parotidectomy to monitoring course of facial nerve. RESULTS Tumor mixtus was a dominate type of tumors. Only three patients with malignant tumor had facial nerve paralysis after surgery. CONCLUSIONS (1) The extent of the surgical procedure depends on histopathologic diagnosis. (2) Using of facial nerve monitoring during parotid surgery improves its outcomes.Summary Introduction Tumors of parotid gland represent a diverse group of neoplasms with varied clinical behaviors. Material and methods The diagnostic methods and treatment of salivary gland tumors are presented in this paper. The authors describe the group of 44 patients with salivary gland tumors treated surgically in ENT Departament Laryngology of Medical University in Łodź. Enucleation, partial and total parotidectomy were performed. Neurosign 100 unit was used during parotidectomy to monitoring course of facial nerve. Results Tumor mixtus was a dominate type of tumors. Only three patients with malignant tumor had facial nerve paralysis after surgery. Conclusions 1. The extent of the surgical procedure depends on histopathologic diagnosis. 2. Using of facial nerve monitoring during parotid surgery improves its outcomes.

The − 5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that -5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer.

Autofluorescencja tkankowa w diagnostyce i ocenie skuteczności leczenia nowotworów głowy i szyi

Summary There are still serious diagnostic and therapeutic challenges in case of carcinoma of the larynx, pharynx and oral cavity most often in patients after radiotherapy. An appropriate choice of a site to take a specimen for histopathology is crucial with regard to establish a diagnosis and find an origin of primary lesion and local recurrence. In this regard our attention is focused on those diagnostic methods which enable to detect even small pathologic lesions. Among them is tissue autofluorescence (DAFE). Its advantages are non-invasiveness, high sensitivity and repeatability. The aim of the study was to validate DAFE as a method for early diagnosis and monitoring of treatment efficacy of head and neck cancers. Forty seven patients were included. Each patient had a fibroscopic investigation with the use of white light and light inducing the tissue fluorescence. A specimen for the histopathology was taken from each site which showed fluorescence in order to verify the diagnosis. The presence of neoplastic lesions was always confirmed with histopathology in parallel with the assessment of the lesion area with fluorescence. DAFE is a non-invasive and useful method for the detection of early cancer lesions with the potential to assess the advances of the disease and to monitor its progress.

Choroba Castlemana – opis przypadku ☆ ☆☆ ◊

Summary The Castleman disease was described for the first time in 1956 by Castleman. It is a rare disease of the lymphatic tissue, manifesting in excessive proliferation of lymphocites B and plasmatic cells in lymph nodes. The etiopathogenesis if the disease still is unknown. The paper presents a case of the Castlemana disease (hyaline vascular type) in 20-year old man with unilateral enlargement of neck lymph nodes. The case exemplifies the difficulties met in diagnostics and treatment of the Castleman disease.

Does the presence of sentinel lymph node macrometastases in breast cancer patients require axillary lymph node dissection?—Single-center analysis

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long‐term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow‐up time for patients after ALND was 36.2 months (6‐74 months); 18.8 months (6‐38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6‐74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long‐term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.