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Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6A NUC vs. ER r = 0.2373 and KAT6B NUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies., (© 2024. The Author(s).)

Epithelial-to-mesenchymal transition (EMT) is a complex cellular process that allows cells to change their phenotype from epithelial to mesenchymal-like. Type 3 EMT occurs during cancer progression. The aim of this study was to investigate the role of RNA-binding motif single-stranded interacting protein 3 (RBMS 3) in the process of EMT. To investigate the impact of RBMS 3 on EMT, we performed immunohistochemical (IHC) reactions on archived paraffin blocks of invasive ductal breast carcinoma ( n = 449), allowing us to analyze the correlation in expression between RBMS 3 and common markers of EMT. The IHC results confirmed the association of RBMS 3 with EMT markers. Furthermore, we performed an in vitro study using cellular models of triple negative and HER-2-enriched breast cancer with the overexpression and silencing of RBMS 3. RT-qPCR and Western blot methods were used to detect changes at both the mRNA and protein levels. An invasion assay and confocal microscopy were used to study the migratory potential of cells depending on the RBMS 3 expression. The studies conducted suggest that RBMS 3 may potentially act as an EMT-promoting agent in the most aggressive subtype of breast cancer, triple negative breast cancer (TNBC), but as an EMT suppressor in the HER-2-enriched subtype. The results of this study indicate the complex role of RBMS 3 in regulating the EMT process and present it as a future potential target for personalized therapies and a diagnostic marker in breast cancer.

The transcription factor hypoxia inducible factor-1 (HIF-1) is one of the main factors in the cell's response to a lack of oxygen. Hypoxia is a typical feature of a growing cancerous tumor. Increased activity of HIF-1 is observed in many cancers, including endometrial cancer. HIF-1 functions as a heterodimer consisting of three subunits HIF-1α, HIF-2α, and HIF-3α and one subunit β. HIF-1α is a subunit that is sensitive to oxygen concentration and is constitutively expressed. The HIF-1α gene is highly polymorphic. Literature data suggest that single nucleotide polymorphisms (SNPs) of the HIF-1α gene may be risk factors for endometrial cancer. A better understanding of the molecular mechanisms of cancer development, progression and prognosis, including the role of SNPs, could lead to the development of new anti-cancer therapies., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The aim of this study was to analyze rs2234693 and rs9340799 polymorphisms of the ESR1 gene in the context of breast cancer risk in Polish patients., Materials and Methods: The study involved a group of 117 patients with breast cancer and 106 controls. The analyses were carried out using the polymerase chain reaction - restriction fragments length polymorphism technique., Results: The presence of the CC genotype in rs2234693 more than doubled the risk of breast cancer (p=0.04), whereas the presence of the TT genotype in rs2234693 significantly reduced the risk of developing this type of cancer (p=0.0002). The presence of the GG genotype in rs9340799 more than doubled the risk of breast cancer (p=0.04), which was confirmed by the analysis of the recessive model (p=0.04)., Conclusion: The polymorphisms rs2234693 and rs9340799 of the ESR1 gene may be associated with the risk of breast cancer among Polish women., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents., Competing Interests: None., (AJCR Copyright © 2024.)

A checkpoint protein called the V-domain Ig suppressor of T cell activation (VISTA) is important for controlling immune responses. Immune cells that interact with VISTA have molecules, or receptors, known as VISTA receptors. Immune system activity can be modified by the interaction between VISTA and its receptors. Since targeting VISTA or its receptors may be beneficial in certain conditions, VISTA has been studied in relation to immunotherapy for cancer and autoimmune illnesses. The purpose of this study was to examine the expression levels and interactions between VISTA and its receptors, VSIG3 and PSGL-1, in breast cancer tissues. IHC analysis revealed higher levels of proteins within the VISTA/VSIG3/PSGL-1 axis in cancer tissues than in the reference samples (mastopathies). VISTA was found in breast cancer cells and intratumoral immune cells, with membranous and cytoplasmic staining patterns. VISTA was also linked with pathological grade and VSIG3 and PSGL-1 levels. Furthermore, we discovered that the knockdown of one axis member boosted the expression of the other partners. This highlights the significance of VISTA/VSIG3/PSGL-1 in tumor stroma and microenvironment remodeling. Our findings indicate the importance of the VISTA/VSIG3/PSGL-1 axis in the molecular biology of cancer cells and the immune microenvironment., (© 2024. The Author(s).)

The coordinated action of VEGF, IGF1/2 and H19 factors influences the development of endometriosis. The aim of this study was to analyze the expression level of these genes in patients with endometriosis. The study group consisted of 100 patients who were diagnosed with endometriosis on laparoscopic and pathological examination. The control group consisted of 100 patients who were found to be free of endometriosis during the surgical procedure and whose eutopic endometrium wasnormal on histopathological examination. These patients were operated on for uterine fibroids. Gene expression was determined by RT-PCR. The expression of the VEGF gene was significantly higher in the samples classified as clinical stage 1-2 compared to the control material ( p < 0.05). There was also a statistically significant difference between the samples studied at clinical stages 1-2 and 3-4 ( p < 0.01). The expression of the VEGF gene in the group classified as 1-2 was significantly higher. IGF1 gene expression was significantly lower both in the group of samples classified as clinical stages 1-2 and 3-4 compared to the control group ( p < 0.05 in both cases). The expression of the H19 gene was significantly lower in the group of samples classified as clinical stage 3-4 compared to the control group ( p < 0.01). The reported studies suggest significant roles of VEGF , IGF and H19 expression in the pathogenesis of endometriosis.

Significant relationships with endometrial cancer were demonstrated, both for CCL2 , CCL5 , and CXCL8 chemokines and for the chemokine receptor CXCR2 . The reported case-control study of genetic associations was designed to establish the role of selected single nucleotide polymorphisms (SNPs) of the CCL2 , CCL5 , CXCL8 , and CXCR2 genes in the onset and progression of endometrial cancer. This study was conducted on 282 women, including 132 (46.8%) patients with endometrial cancer and 150 (53.2%) non-cancerous controls. The genotypes for CCL2 rs4586, CCL5 rs2107538 and rs2280789, CXCL8 rs2227532 and -738 T>A, and CXCR2 rs1126580 were determined, using PCR-RFLP assays. The AA homozygotes in CCL5 rs2107538 were associated with more than a quadruple risk of endometrial cancer ( p ≤ 0.050). The GA heterozygotes in the CXCR2 SNP were associated with approximately threefold higher cancer risk ( p ≤ 0.001). That association also remained significant after certain adjustments, carried out for age, diabetes mellitus, arterial hypertension, or endometrial thickness above 5 mm ( p ≤ 0.050). The A-A haplotypes for the CCL5 polymorphisms and T-A-A haplotypes for the CCL2 and CCL5 SNPs were associated with about a twofold risk of endometrial cancer ( p ≤ 0.050). In conclusion, CCL2 rs4586, CCL5 rs2107538 and rs2280789, and CXCR2 rs1126580 demonstrated significant associations with an increased risk of endometrial cancer.

Irisin (Ir) is an adipomyokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. Additionally, FNDC5/Ir is suspected of inhibiting the epithelial-mesenchymal transition (EMT) process. This relationship has been poorly studied for breast cancer (BC). The ultrastructural cellular localizations of FNDC5/Ir were examined in BC tissues and BC cell lines. Furthermore, we compared serum levels of Ir with FNDC5/Ir expression in BC tissues. The aim of this study was to examine the levels of EMT markers, such as E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST, and to compare their expression levels with FNDC5/Ir in BC tissues. Tissue microarrays with 541 BC samples were used to perform immunohistochemical reactions. Serum levels of Ir were assessed in 77 BC patients. We investigated FNDC5/Ir expression and ultrastructural localization in MCF-7, MDA-MB-231, and MDA-MB-468 BC cell lines and in the normal breast cell line (Me16c), which was used as the control. FNDC5/Ir was present in BC cell cytoplasm and tumor fibroblasts. FNDC5/Ir expression levels in BC cell lines were higher compared to those in the normal breast cell line. Serum Ir levels did not correlate with FNDC5/Ir expression in BC tissues but were associated with lymph node metastasis (N) and histological grade (G). We found that FNDC5/Ir correlated moderately with E-cadherin and SNAIL. Higher Ir serum level is associated with lymph node metastasis and increased grade of malignancy. FNDC5/Ir expression is associated with E-cadherin expression level.

Deep infiltrating endometriosis (DIE) is characterized by the presence of endometrial tissue outside the uterine cavity that infiltrates at least 5-mm deep below the peritoneal layer. Imagining examinations are the first-choice methods to detect DIE. The aim of this study is to assess whether rectal water contrast transvaginal sonography (RWC-TVS) can be a useful tool for the estimation of the size of deep bowel endometriotic nodules. This retrospective study includes 31 patients subjected to RWC-TVS who underwent surgery due to deep bowel endometriosis between January 2021 and December 2022. Nodule dimensions measured via ultrasound were compared to those of histopathological samples taken after surgery. In total, 52% of patients had endometriosis limited only to the intestines, 19% had endometriotic nodules located at uterosacral ligaments and posterior vaginal fornix, 6% at the anterior compartment, and 13% at a different location. Additionally, 6% of patients had nodules at more than two locations. In all but one case, the intestinal nodules could be seen on RWC-TVS images. The largest nodule dimension measured via RWC-TVS and the size of the equivalent histopathological sample correlated (R = 0.406, p = 0.03). Thus, RWC-TVS allows for the detection of DIE and moderate estimation of the nodule sizes and should be practiced during a diagnostic process.

In the epithelial-mesenchymal transition (EMT) process, cells lose their epithelial phenotype and gain mesenchymal features. This phenomenon was observed in the metastatic phase of neoplastic diseases, e.g., cervical cancer. There are specific markers that are expressed in the EMT. The aim of this study was to determine the localization of and associations between the immunohistochemical (IHC) expression of TWIST, SNAIL, and SLUG proteins in precancerous lesions and cervical cancer. The IHC analysis disclosed higher expressions of EMT markers in precancerous lesions and cervical cancer than in the control group. Moreover, stronger expression of TWIST, SNAIL, and SLUG was observed in cervical intraepithelial neoplasia grade 3 (CIN3) vs. CIN1, CIN3 vs. CIN2, and CIN2 vs. CIN1 cases ( p < 0.05). In cervical cancer, IHC reactions demonstrated differences in TWIST, SNAIL, and SLUG expression in grade 1 (G1) vs. grade 2 (G2) ( p < 0.0011; p < 0.0017; p < 0.0001, respectively) and in G1 vs. grade 3 (G3) ( p < 0.0029; p < 0.0005; p < 0.0001, respectively). The results of our study clearly showed that existing differences in the expression of the tested markers in precancerous vs. cancerous lesions may be utilized in the diagnosis of cervical cancer. Further studies on bigger populations, as well as in comparison with well-known markers, may improve our outcomes.

Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM is characterized by an infiltrating growth nature, abundant vascularization, and a rapid and aggressive clinical course. For many years, the standard treatment of gliomas has invariably been surgical treatment supported by radio- and chemotherapy. Due to the location and significant resistance of gliomas to conventional therapies, the prognosis of glioblastoma patients is very poor and the cure rate is low. The search for new therapy targets and effective therapeutic tools for cancer treatment is a current challenge for medicine and science. microRNAs (miRNAs) play a key role in many cellular processes, such as growth, differentiation, cell division, apoptosis, and cell signaling. Their discovery was a breakthrough in the diagnosis and prognosis of many diseases. Understanding the structure of miRNAs may contribute to the understanding of the mechanisms of cellular regulation dependent on miRNA and the pathogenesis of diseases underlying these short non-coding RNAs, including glial brain tumors. This paper provides a detailed review of the latest reports on the relationship between changes in the expression of individual microRNAs and the formation and development of gliomas. The use of miRNAs in the treatment of this cancer is also discussed., Competing Interests: The authors declare no conflict of interest.

The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues ( p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens ( p < 0.05) and ER(-) cancer specimens ( p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells ( p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines ( p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell−cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

Background: Endometriosis is a chronic disease of the genital organs that mainly affects women of reproductive age. The analysis of long non-coding RNA (lncRNA) in endometriosis is a novel field of science. Recently, attention has been drawn to SNHG4 , which is incorrectly expressed in various human diseases, including endometriosis., Aim: The aim of this pilot study was to analyze the expression of lncRNA small nucleolar RNA host gene 4 ( SNHG4 ) and to investigate its significance in endometriosis., Material and Methods: LncRNA SNHG4 expression was investigated in paraffin blocks in endometriosis patients (n = 100) and in endometriosis-free controls (n = 100) using a real-time PCR assay., Results: This study revealed a higher expression of SNHG4 in endometriosis patients than in controls. A statistically significant relationship between expression level and SNHG4 was found in relation to The Revised American Society for Reproductive Medicine classification of endometriosis, 1996, in the group of patients with endometriosis., Conclusion: This pilot study has revealed that gene expression in SNHG4 plays an important role in the pathogenesis of endometriosis.

Endometriosis is a disease of the female genital organs, the causes of which are not fully understood. Recent studies have shown that non-coding RNAs (ncRNAs) like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) can contribute to the pathogenesis of endometriosis. Profiling of miRNA and lncRNA expression is carried out using state-of-the-art molecular biology techniques (RT-PCR, sequencing, microarray analysis). The use of the latest technologies may make it possible to establish a genetic profile, which is a promising prospect for early diagnosis of endometriosis. In the future, genetic testing may become the gold diagnostic standard and eliminate invasive laparoscopy. In the case of endometriosis, it is important to extend the research to molecular aspects, which may facilitate the diagnosis of the disease or indicate new (based for example ncRNA) treatment methods. The paper presents the latest data on the importance of miRNA/lncRNA in endometriosis.

Endometriosis is a disease of complex etiology. Hormonal, immunological, and environmental factors are involved in its formation. In recent years, special attention has been paid to genetic mechanisms that can have a significant impact on the increased incidence of endometriosis. The study aimed to analyze the expression of four long non-coding RNA (lncRNA) genes, UCA1, MALAT1, TC0101441, and H19, in the context of the risk of developing endometriosis. The material for genetic testing for the expression of lncRNA genes were tissue slices embedded in paraffin blocks from patients with endometriosis ( n = 100) and the control group ( n = 100). Gene expression was determined by the RT-PCR technique. The expression of the H19 gene in endometriosis patients was statistically significantly lower than in the control group. A statistically significant association was found between H19 gene expression in relation to The Revised American Society for Reproductive Medicine classification of endometriosis (rASRM) in the group of patients with endometriosis. Research suggests that H19 expression plays an important role in the pathogenesis of endometriosis.

Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

Recently, many studies have shown that microRNAs (miRNAs) in extracellular bioliquids are strongly associated with subarachnoid hemorrhage (SAH) and its complications. The article presents issues related to the occurrence of subarachnoid hemorrhage (epidemiology, symptoms, differential diagnosis, examination, and treatment of the patient) and a review of current research on the correlation between miRNAs and the complications of SAH. The potential use of miRNAs as biomarkers in the treatment of SAH is presented.

Breast cancer is the most-commonly diagnosed malignant tumor in women in the world, as well as the first cause of death from malignant tumors. The incidence of breast cancer is constantly increasing in all regions of the world. For this reason, despite the progress in its detection and treatment, which translates into improved mortality rates, it seems necessary to look for new therapeutic methods, and predictive and prognostic factors. Treatment strategies vary depending on the molecular subtype. Breast cancer treatment is multidisciplinary; it includes approaches to locoregional therapy (surgery and radiation therapy) and systemic therapy. Systemic therapies include hormone therapy for hormone-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, and quite recently, immunotherapy. Triple negative breast cancer is responsible for more than 15-20% of all breast cancers. It is of particular research interest as it presents a therapeutic challenge, mainly due to its low response to treatment and its highly invasive nature. Future therapeutic concepts for breast cancer aim to individualize therapy and de-escalate and escalate treatment based on cancer biology and early response to therapy. The article presents a review of the literature on breast carcinoma-a disease affecting women in the world.

Background: MicroRNAs (miRNAs) are small RNA molecules involved in the control of the expression of many genes and are responsible for, among other things, cell death, differentiation and the control of their division. Changes in miRNA expression profiles have been observed in colorectal cancer. This discovery significantly enriches our knowledge of the pathogenesis of colorectal cancer and offers new goals in diagnostics and therapy., Aim: The aim of this study was to analyze the expression of four miRNA sequences-miR-143, miR-1, miR-210 and let-7e-and to investigate their significance in the risk of developing colorectal cancer., Materials and Methods: miRNA sequences were investigated in formalin-fixed, paraffin-embedded (FFPE) tissue in colorectal cancer patients ( n = 150) and in cancer-free controls ( n = 150). The real-time PCR method was used., Results: This study revealed a lower expression of miR-143 in colorectal cancer patients than in the controls. miR-143 was positively correlated with the degree of tumor differentiation (grading). Three out of four analyzed miRNA (miR-1, miR-210 and let-7e) were found to be statistically insignificant in terms of colorectal carcinoma risk., Conclusions: miR-143 may be associated with the development of colorectal cancer.

Background: The analysis of long non-coding RNA (lncRNA) in endometrial cancer is a novel field of science. Although numerous lncRNA sequences have been identified until today, their correlation with endometrial cancer is still undetermined. The aim of this study was to analyze the expression of four lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 and to investigate their significance in endometrial cancer., Methods: LncRNA sequences were investigated in paraffin blocks (tumor tissue and non-malignant endometrial tissue in archival postoperative specimens) in endometrial cancer patients (Cases, n = 120) and in cancer-free controls (n = 80) using real-time PCR assay., Results: This study revealed a lower expression of LINC01468 in endometrial cancer patients than in controls. Both LINC01468 and FAM3D-AS1 were positively correlated with Body Mass Index (BMI) in cancer-free controls., Conclusions: LncRNA LINC01468 may be a protective factor in development of endometrial cancer., (© 2022. The Author(s).)

Background. The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer. Aim. The presented work assessed the expression of two transcribed-ultra conserved regions−uc.63 and uc.38−in breast cancer tissue samples. Material and methods. The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group). Results. As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient’s age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035). Conclusion. The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.

Irisin is a myokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. FNDC5 and irisin levels have been poorly studied in the tumor tissues of breast cancer (BC). The aim of this study was to determine the levels of irisin expression in BC tissues and compare them to clinicopathological factors and Ki-67 and PGC-1α expression levels. Tissue microarrays (TMAs) with 541 BC tissues and 61 samples of non-malignant breast disease (NMBD; control) were used to perform immunohistochemical reactions. FNDC5 gene expression was measured in 40 BC tissue samples, 40 samples from the cancer margin, and 16 NMBD samples. RT-PCR was performed for the detection of FNDC5 gene expression. Higher irisin expression was found in BC patients compared to normal breast tissue. FNDC5/irisin expression was higher in patients without lymph node metastases. Longer overall survival was observed in patients with higher irisin expression levels. FNDC5/irisin expression was increased in BC tissues and its high level was a good prognostic factor for survival in BC patients.

MicroRNAs (miRNAs) are short, noncoding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level by binding to mRNAs. miRNAs affect the course of processes of fundamental importance for the proper functioning of the organism. These processes include cell division, proliferation, differentiation, cell apoptosis and the formation of blood vessels. Altered expression of individual miRNAs has been shown in numerous cancers, which may indicate the oncogenic or suppressor potential of the molecules in question. This paper discusses the current knowledge about the possibility of using miRNA as a diagnostic marker and a potential target in modern anticancer therapies.

Objective: Although polymorphisms of adiponectin gene ( ADIPOQ ) in obesity-related conditions have been the target of research efforts, little is known about this genetic marker in uterine leiomyomas. The aim of this pilot study was to analyze the frequencies of alleles and genotypes of Single Nucleotide Polymorphism ADIPOQ (NM&#95;004797.4):c.214+62G>T (rs1501299) and to correlate it with the risk of uterine fibroids. Study Design: The Test Group comprised 90 women treated surgically for uterine leiomyomas in the Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother's Memorial Hospital-Research Institute. 90 disease-free individuals were used as Controls. Patients within both groups were additionally stratified into lean, overweight and obese, according to Body Mass Index. Statistical analysis was performed between the two major groups and, furthermore, within the abovementioned subgroups. Results: The study revealed no statistically significant differences in the distribution of alleles and genotypes of SNP ADIPOQ (NM&#95;004797.4):c.214+62G>T (rs1501299) between the two main groups. A weak correlation within distributions of alleles was observed between obese Test Patients and lean Controls. Conclusion: This pilot study has revealed no association between SNP ADIPOQ (NM&#95;004797.4):c.214+62G>T (rs1501299) and uterine fibroids. Further studies on larger groups are warranted to elucidate whether this SNP may be correlated with uterine leiomyomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bieńkiewicz, Smolarz, Wilczyński, Stepowicz, Jabłoński, Obłękowska, Malinowski and Romanowicz.)

Objective: Epilepsy is a neurologically based disease. Literature data indicate a certain association between the polymorphism of these genes, which participate in the metabolism of drugs (CYP), and drug-resistant epilepsy., Aim: The reports describe studies in which an association was evaluated between the rs1799853 (430C > T) and rs1057910 (1075A > C) polymorphisms of CYP2C9 gene and the rs4244285 (c.681G > A) polymorphism of CYP2C19 gene on one hand and the incidence of drug-resistant epilepsy in children on the other., Material and Methods: The above-mentioned polymorphisms were assessed by the PCR-RFLP technique in a group of patients with drug-resistant ( n  = 106) and drug-responsive ( n  = 80) epilepsy, as well as in non-epileptic children ( n  = 97), all of them hospitalised at the Department of Neurology of the Institute-Polish Mother's Memorial Hospital in Lodz., Results: It was demonstrated that CT genotype of the rs1799853 polymorphism of CYP2C9 gene and GA genotype of the rs4244285 polymorphism of CYP2C19 gene caused an enhanced risk of epilepsy. It was also shown that the occurrence of C-G-A haplotype, when referred to the rs1799853 polymorphism of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene, could be associated with a decreased risk of epilepsy occurrence. In case of the rs1799853 polymorphism in CYP2C9 gene, the occurrence of T allele four times increases the risk of drug-resistance in patients with diagnosed epilepsy., Conclusion: The obtained results indicated that the rs1799853 and rs1057910 polymorphisms of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene could be associated with the occurrence of drug-resistant epilepsy in children.

Pharmacogenomic studies in epilepsy are justified by the high prevalence rate of this disease and the high cost of its treatment, frequent drug resistance, different response to the drug, the possibility of using reliable methods to assess the control of seizures and side effects of antiepileptic drugs. Candidate genes encode proteins involved in pharmacokinetic processes (drug transporters, metabolizing enzymes), pharmacodynamic processes (receptors, ion channels, enzymes, regulatory proteins, secondary messengers) and drug hypersensitivity (immune factors). This article provides an overview of the literature on the influence of genetic factors on treatment in epilepsy.

Endometriosis is a "mysterious" disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic, autoimmune and allergic factors are listed. It is believed that the primary mechanism of the formation of endometriosis foci is retrograde menstruation, i.e., the passage of menstrual blood through the fallopian tubes into the peritoneal cavity and implantation of exfoliated endometrial cells. However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci. Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life. It also represents a significant financial burden on health systems. The article presents a review of the literature on endometriosis-a disease affecting women throughout the world.

MicroRNAs (miRNAs) are small ribonucleic acid molecules that play a key role in regulating gene expression. The increasing number of studies undertaken on the functioning of microRNAs in the tumor formation clearly indicates their important potential in oncological therapy. Pancreatic cancer is one of the deadliest cancers. The expression of miRNAs released into the bloodstream appears to be a good indicator of progression and evaluation of the aggressiveness of pancreatic cancer, as indicated by studies. The work reviewed the latest literature on the importance of miRNAs for pancreatic cancer development.

Background: The aim of this study was to analyze the frequencies of genotypes and alleles of Single Nucleotide Polymorphism (SNP) LEP-R c.668A>G (p.Gln223Arg, rs1137101) of leptin receptor gene and to assess the influence this DNA marker has on endometrial cancer (EC) with respect to total body fat content., Methods: The study comprised 120 patients treated for endometrial cancer and 90 controls treated for uterine fibroids. In total, 210 patients were included in this research. DNA was isolated from archival post-operative specimens. Polymerase Chain Reaction - Restriction Fragment Length Polymorphism was employed to analyze the SNP., Results: In this paper we have demonstrated that heterozygous genotype AG of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) is statistically less frequent in women with endometrial cancer (EC) than in controls: 33 versus 57%, respectively. Similarly, this heterozygous genotype is statistically significantly less frequent in obese (BMI > 30) women with EC than in lean controls (BMI < 25): 30 versus 63%, respectively., Conclusions: AG polymorphic variant of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) in LEP-R may be considered a protective factor in the development of endometrial cancer., (© 2021. The Author(s).)

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group ( p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group ( p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

Long noncoding RNAs (lncRNAs) are the largest groups of ribonucleic acids, but, despite the increasing amount of literature data, the least understood. Given the involvement of lncRNA in basic cellular processes, especially in the regulation of transcription, the role of these noncoding molecules seems to be of great importance for the proper functioning of the organism. Studies have shown a relationship between disturbed lncRNA expression and the pathogenesis of many diseases, including cancer. The present article presents a detailed review of the latest reports and data regarding the importance of lncRNA in the development of cancers, including breast carcinoma.

Purpose: Endometriosis is a frequent gynaecological condition, both in Poland and in the world. The development of this disease is supported by hormonal, immunological and environmental factors. During the recent years, a particular attention has been focused on the genetic polymorphisms which may be of particular significance for the increased incidence rates of endometriosis. According to literature data, Oestrogen Receptor 2 (ESR2) and Cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) genes may be accounted to the potential risk factors of infertility associated with endometriosis. The reported research was aimed to evaluate the association between single nucleotide polymorphisms (SNPs) rs17179740 of ESR2 and rs2899470 of CYP19A1 genes and the incidence of endometriosis., Methods: The study material included blood specimens, collected from patients (n = 200) with endometriosis. Blood samples from age-matched, endometriosis-free women (n = 200) served as control. The High-Resolution Melter (HRM) technique was applied for polymorphism analysis., Results: Regarding rs2899470 polymorphism TT homozygotes was significantly more prevalent among the patients with endometriosis than in the controls (OR 2.19; p = 0.04). In case of rs17179740, GG homozygotes, as well as AG-AA genotypes, were significantly more prevalent among the endometriosis patients (OR 2.48, p = 0.04 and OR 2.36, p = 0.04, respectively)., Conclusion: Summing up, the investigated polymorphisms of ESR2 and CYP19A1 gene are associated with the observed incidence of endometriosis., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immunological disorders, increased oxidative stress, and damage to the epithelial barrier play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). In the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC), it is increasingly common to use biological drugs that selectively affect individual components of the inflammatory cascade. However, administering the medicines currently available does not always result in obtaining and maintaining remission, and it may also lead to the development of resistance to a given agent over time. Metallothioneins (MTs) belong to the group of low molecular weight proteins, which, among others, regulate the inflammation and homeostasis of heavy metals as well as participating in the regulation of the intensity of oxidative stress. The results of the studies conducted so far do not clearly indicate the role of MTs in the process of inflammation in patients with IBD. However, there are reports that suggest the possibility of using MTs as a potential target in the treatment of this group of patients., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Anna Socha-Banasiak et al.)

Aim of the Study: The aim of the study was to analyze three single nucleotide polymorphisms - rs1520220, rs2946834, rs6219 - of the IGF-1 gene in the context of breast mammographic density., Material and Methods: The research material included 202 samples of the peripheral blood of women with increased mammographic breast density and 238 samples of the epithelium from the oral mucosa of women without diagnosed pathological changes of the breast and with no family history of breast and/or ovarian cancer. The real-time polymerase chain reaction method was applied for analysis of polymorphisms., Results: rs1520220 polymorphism was associated with increased mammographic density of the breasts. The presence of the CC genotype in the IGF-1 gene increased the risk of developing higher breast density visible in mammography by 2.43-fold. CC homozygotes (rs1520220) correlated with higher Breast Imaging-Reporting and Data System scale (3 vs. 4 and 5) (OR = 5.6; 95% CI: 1.82-16.3, p = 0.001). In the present study no relationship was detected between rs6219 and rs2946834 polymorphism and mammographic breast density., Conclusions: The results suggest that the rs1520220 polymorphism of the IGF-1 gene plays an important role in the occurrence of increased mammographic breast density., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Termedia.)

Aim of the Study: To analyze six single nucleotide polymorphisms (SNPs): rs1520220, rs2945834, rs5747694, rs6214, rs6219, rs5742678. An attempt was made to assess the significance of the above IGF-1 gene polymorphisms as prognostic and predictive factors in Polish women with diagnosed increased breast mammographic density., Material and Methods: The study included women diagnosed with an increased breast mammographic density ( n = 98), breast cancer ( n = 135) and women as a control group ( n = 60). The method used to detect polymorphisms in the IGF-1 gene was the analysis of single-stranded DNA conformation polymorphism (SSCP-PCR) and Sanger's sequencing., Results: In the case of rs1520220 polymorphism, the genotype CC was found to increase the risk of breast cancer (OR = 2.6 95% CI 1.01-6.5, p = 0.04). Analysis of the rs2945834 polymorphism revealed that the occurrence of the G allele reduced the risk of breast cancer, while the occurrence of the A allele increased the risk of disease almost twice (OR = 0.55 95% CI). Among women who are heterozygous in terms of rs5747694 polymorphism (TG), the risk of breast cancer is twice as high as in the control group. The SNPs in the study group did not correlate with mammographic breast density., Conclusions: The results obtained in the course of the analysis indicate that polymorphisms rs1520220, rs2946834, rs5747694 gene IGF-1 are associated with the occurrence of breast cancer but not with increased mammographic density. Summing up, the association between the polymorphisms of IGF-1 and the risk of developing breast cancer is independent of mammographic density., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Endometriosis is defined as the presence of endometrial foci, localized beyond their primary site, i.e., the uterine cavity. The etiology of this disease is rather complex. Its development is supported by hormonal, immunological, and environmental factors. During recent years, particular attention has been focused on the genetic mechanisms that may be of particular significance for the increased incidence rates of endometriosis. According to most recent studies, ESR2 and CYP19A1 genes may account for the potential risk factors of infertility associated with endometriosis. The paper presents a thorough review of the latest reports and data concerning the genetic background of the risk for endometriosis development.

High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients' clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer cell lines (A2780, A2780cis, SK-OV-3, OVCAR3). We assessed the relative expression of miRNA-103/107 (quantitative reverse transcription-polymerase chain reaction) in fifty archival formalin-fixed paraffin-embedded tissue samples of primary high grade serous ovarian cancer. Then, miRNA-103/107 and DICER expression levels were evaluated in selected ovarian cancer cell lines. Additionally, DICER, N-/E-cadherin protein levels were assessed with the use of western blot. We identified miRNA-107 up-regulation in ovarian cancer in comparison to healthy tissues ( p = 0.0005). In the case of miRNA-103, we did not observe statistically significant differences between cancerous and healthy tissues ( p = 0.07). We did not find any correlations between miRNA-103/107 expression levels and clinicopathological features. Kaplan-Meier survival (disease-free and overall survival) analysis revealed that both miRNAs could not be considered as prognostic factors. SK-OV-3 cancer cell lines were characterized by high expression of miRNA-103/107, relatively low expression of DICER (western-blot), and relatively high N-cadherin levels in comparison to other ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study.

Aim: The analysis of oestrogen receptor (ESR2) and cytochrome P450 family 19 subfamily A member (CYP19A1) gene expression in the context of the risk for endometriosis development., Materials and Methods: Tissue specimens, collected from patients with endometriosis (n=100) and from control patients (n=100) embedded into paraffin blocks, provided the material for genetic studies, oriented towards the expression of ESR2 and CYP19A1 genes. The gene expression was assessed by the reverse transcription-polymerase chain reaction technique., Results: Higher expression levels of ESR2 gene were demonstrated in the patients with endometriosis in comparison with the healthy controls. The expression intensity of CYP19A1 gene was associated with endometriosis, manifested as abdominal wall nodules. A relationship was observed between CYP19A1 gene expression and the Revised American Society for Reproductive Medicine classification in the group with ovarian endometrioid cysts, as well as in the group with peritoneal endometriosis., Conclusion: This study suggests the significant role of ESR2 and CYP19A1 gene expression in the pathogenesis of endometriosis., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: ESR2 and CYP19A1 genes play a major role in the hormonal control of women with endometriosis. The aim of the study was to analyze single nucleotide polymorphisms (SNPs) in the 3'UTR region of ESR2 and CYP19A1 genes. The study aimed at localisation of new polymorphisms, the nucleotide variants of which determine the level of susceptibility to endometriosis., Study Design: The study included n = 200 patients: 100 with endometriosis and 100 healthy controls. The Sanger's sequencing method was applied for polymorphism analysis., Results: Statistically significant correlations were identified between new, not previously described, two SNPs of ESR2 gene and endometriosis: rs4986938 (G>A) and rs928554 (A>G). In the case of rs4986938 polymorphism, the genotype AA was found to decrease the risk of endometriosis (OR = 0.24 95 % PU 0.05-1.22, p = 0.04). Analysis of the rs928554 polymorphism revealed that the occurrence of the AG genotype reduced the risk of endometriosis (OR = 0.38 95 % PU 0.21-0.71, p = 0.002). There were no differences in the distribution of genotypes of the polymorphisms rs10046 (C>T) and rs4646 (C>A) of CYP19A1 gene between patients and control., Conclusions: Further studies are necessary in groups with higher numbers of patients to explain whether the above-mentioned polymorphisms may be the risk factors for endometriosis., Competing Interests: Declaration of Competing Interest All the authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: This research was aimed to evaluate the association between three selected single nucleotide polymorphisms (SNPs) within the CDKN2A (P14ARF) tumour suppressor gene and the incidence of endometrial cancer (EC) in postmenopausal women., Patients and Methods: The study included 194 postmenopausal women; 144 with EC and 50 non-cancer controls. Genotypes in P14ARF rs3088440, rs3731217 and rs3731245 polymorphisms were assayed using PCR-RFLP and confirmed by sequencing., Results: Regarding the rs3088440 polymorphism, CT, and CT-TT genotypes, were more prevalent among EC patients than in controls (OR=5.55, p=0.023, OR=5.29, p=0.027; and OR=2.92, p=0.023, respectively). The T allele within rs3088440 was more prevalent in EC females than in controls (χ 2 =4.7, p=0.030). Considering rs3731217, TG and TG-GG genotypes were less prevalent among EC (OR=0.34, p=0.024 or p=0.023; and OR=0.38, p=0.035, respectively)., Conclusion: Polymorphisms in the CDKN2A gene are associated with EC in postmenopausal women., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Single nucleotide polymorphisms (SNPs) may modify the risk of cancer. They may be then regarded as potential markers of carcinogenesis. The aim of this study was to analyze the frequency of genotypes and alleles of SNPs in DNA repair genes and to investigate the influence this genetic variation exerts on breast cancer in Polish females. The test group comprised 600 females with breast cancer and 600 healthy controls. Genomic DNA was isolated and the SNPs in DNA repair genes were determined by High-Resolution Melter (HRM) technique. Following polymorphisms were analysed: Arg399Gln (rs25487) of the XRCC1, Gly322Asp (rs4987188) of the hMSH2, Lys751Gln (rs13181) of the XPD, Arg188His (rs3218536) of the XRCC2, P871L (rs799917) of the BRCA1 and N372H (rs144848) of the BRCA2 gene. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele. Statistically significant correlations were identified between 4 single nucleotide polymorphisms and the breast cancer risk: rs25487 rs4987188 rs13181 and rs799917. The alleles XRCC1-Gln (OR 5.11; 95% CI 5.68-11.64, p < .0001), hMSH2-Asp (OR 4.66; 95% CI 3.90-5.56, p < .0001), XPD-Gln (OR 2.65; 95% CI 2.24-3.14, p < .0001) and BRCA1-L (OR 1.45; 95% CI 1.24-1.71, p < .0001) genes were strongly correlated with this malignancy. No correlation was found between the studied SNPs and tumor grading nor the lymph node status. Further research on larger groups is warranted to determine the influence of above-mentioned genetic variants on breast cancer risk.

Ovarian cancer is one of the most common types of cancer in women. The repair system via homologous recombination repairs double-strand breaks (DSB) of DNA, which are the most mortal for cell, out of all DNA damages. The genes, which encode the double-strand break repairing proteins, are highly polymorphic and, taking into account the significance of the repaired defects for cancer development, it seems important to learn the role of the polymorphisms in ovarian cancer development. The aim of the study was to determine the relationship between DNA repair genes via homologous recombination (HR) and modulation of the risk of ovarian cancer. The following polymorphisms were analysed: XRCC3-Thr241Met (rs861539), XRCC2--41657C/T (rs718282), XRCC2-Arg188His (rs3218536), BRCA1-Q356R (rs1799950) and RAD51-135 G/C (rs1801320). The study group included 600 patients with ovarian cancer and 600 healthy controls. The PCR-RFLP (PCR-based restriction fragment length polymorphism) technique was applied for polymorphism analysis. Allele XRCC3-241Met (OR 0.85, 95%CI 0.72-0.99, p < 0.045), XRCC2-41657 T (OR 1.67, 95% CI 1.42-1.96, p < .0001), BRCA1-356R (OR 1.61; % CI 1.37-1.90, p < .0001) and RAD51-135C (OR 5.16; 95% CI 4.29-6.20, p < .0001) strongly correlated with the neoplastic disease. No relationship was observed between the studied polymorphisms and the cancer progression stage according to FIGO classification. The results indicate that polymorphisms of DNA repair genes via homologous recombination may be associated with the incidence of ovarian cancer. Further research on larger groups is warranted to determine the influence of above-mentioned genetic variants on ovarian cancer risk.

Aim: The aim of the study was to determine the relationship between single nucleotide polymorphisms (SNPs) of DNA repair genes and modulation of the risk of breast cancer. The following SNPs were analysed: XRCC1-Arg399Gln (rs25487), hMSH2-Gly322Asp (rs4987188), XRCC2 -Arg188His (rs3218536), XPD - Lys751Gln (rs13181), RAD51 --4719A/T (rs2619679) and RAD51 --4601A/G (rs5030789)., Material and Methods: The study included n = 600 patients: 300 with breast cancer and 300 healthy controls. The HRM (High-Resolution Melter) technique was applied for polymorphism analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele., Results: Statistically significant correlations were identified between four single nucleotide polymorphisms and the breast cancer risk: XRCC1 -Arg399Gln, hMSH2 -Gly322Asp, XPD - Lys751Gln and RAD51 --4719A/T. Allele XRCC1-Gln (OR 6.37; 95% CI 4.86-8.35, p < .0001), hMSH2 -Asp (OR 4.41; 95% CI 3.43-5.67, p < .0001), XPD -Gln (OR 2.56; 95% CI 2.02-3.25, p < .0001) and RAD51 -T genes (OR 1.44; 95% CI 1.15-1.80, p = 0.002) strongly correlated with breast carcinoma. No relationship was observed between the studied polymorphisms and the cancer progression grade according to Scarf-Bloom-Richardson classification., Conclusions: The results implies that polymorphisms of DNA repair genes may be associated with breast cancer occurrence., Competing Interests: CONFLICTS OF INTEREST Authors declare no conflicts of interest.