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Background Genetic variants in hormone receptor genes may be crucial predisposing factors for breast cancer, and microsatellites in the androgen receptor gene (AR) have been suggested to play a role. The aim of the study was to determine the association between the length of the CAG repeats in the AR gene and the development of breast cancer. Methodology: In total, 75 breast cancer cases and 50 healthy controls were analyzed for CAG repeats in the AR gene by polymerase chain reaction and the GeneScan/Genotyping technique.

Topoisomerase IIb binding protein 1 (TopBP1) is involved in cell survival, DNA replication, DNA damage repair and cell cycle checkpoint control. The biological function of TopBP1 and its close relation with BRCA1 prompted us to investigate whether alterations in the TopBP1 gene can influence the risk of breast cancer. The aim of this study was to examine the association between five polymorphisms (rs185903567, rs116645643, rs115160714, rs116195487, and rs112843513) located in the 30UTR region of the TopBP1 gene and breast cancer risk as well as allele-specific gene expression. Five hundred thirty-four breast cancer patients and 556 population controls were genotyped for these SNPs. Allele-specific Top- BP1 mRNA and protein expressions were determined by using real time PCR and western blotting methods, respectively. Only one SNP (rs115160714) showed an association with breast cancer. Compared to homozygous common allele carriers, heterozygous and homozygous for the T variant had significantly increased risk of breast cancer (adjusted odds ratio = 3.81, 95 % confidence interval: 1.63–8.34, p = 0.001). Mean TopBP1 mRNA and protein expression were higher in the individuals with the CT or TT genotype. There was a significant association between the rs115160714 and tumor grade and stage. Most carriers of minor allele had a high grade (G3) tumors classified as T2-T4N1M0. Our study raises a possibility that a genetic variation of TopBP1 may be implicated in the etiology of breast cancer.

The most lethal damage for the cell among all damage is double-strand breaks (DSB) of DNA. DSB cause development of cancer diseases including the triple-negative mo - lecular subtype of breast cancer. The aim of this work was to evaluate the single nu - cleotide polymorphism -135G>C (rs1801320) of the RAD51 gene encoding DNA repair proteins by homologous recombination (HR) in triple-negative breast cancer (TNBC). We assessed the RAD51 -135G>C polymorphism in 50 women with triple-nega - tive breast cancer and in 50 women from the control group. RAD51 polymorphism was analysed by the PCR-RFLP (restriction fragment length polymorphism) tech - nique. Our results demonstrated a significant positive association between the RAD51 C/C genotype and TNBC, with an adjusted odds ratio (OR) of 5.95 (p = 0.002). The ho - mozygous C/C genotype was found in 68% of breast cancer cases and 20% of con - trols. The variant 135C allele of RAD51 increased TNBC risk. This is the first study linking single nucleotide polymorphisms of the RAD51 gene with TNBC incidence in the population of Polish women. In conclusion, RAD51 poly - morphisms may be regarded as predictive factors of triple-negative breast cancer in the female population. Large studies are needed to confirm our findings.

Sentinel lymph node (SLN) biopsy is a part of the staging procedure in breast cancer patients. Intraoperative molecular analysis for SLN metastases using the one-step nucleic acid amplification (OSNA) method based on reverse-transcription loop-mediated amplification (RT-LAMP) has already been validated in breast cancer. In this study, we compare the intraoperative OSNA method to our routine histological investigation. To evaluate the performance of OSNA in comparison to histology, analysis of 74 SLN from 60 breast cancer patients was conducted with both methods. Of the 22 histologically positive samples, 14 were attributed to macrometastases (++) in the OSNA-CK19 assay and 8 to micrometastases (+). Two samples negative in histopathology were positive in the OSNA method (micrometastases +). Our results show that OSNA is an excellent method for the detection of metastases in lymph nodes and can be applied as an intraoperative diagnostic approach. Intraoperative molecular analysis for SLN metastases using the OSNA method reduces the number of admission days and duration of surgery. To our knowledge this is the first study referring to Polish women.

Metallothioneins (MTs) are a family of metal binding proteins that play an important role in cellular processes such as proliferation and apoptosis. Metallothionein 2A is the most expressed MT isoform in the breast cells. A number of studies have demonstrated increased MT2A expression in various human tumors, including breast cancer. We carried out an association study to examine whether MT2A gene polymorphisms are associated with risk of breast cancer. Information on lifestyle risk factors was collected via a self-administered questionnaire. Genotyping was conducted using polymerase chain reaction–restriction fragment length polymorphism technique. Three single nucleotide polymorphisms (SNP) rs28366003, rs1610216 and rs10636 were genotyped in 534 breast cancer cases and 556 population controls. One SNP in MT2A (rs28366003) showed a positive association with breast cancer. Compared with homozygous common allele carriers, heterozygous for the G variant [odds ratio (OR) = 1.92, 95 % confidence interval (CI):1.28–2.81, p trend

TopBP1 protein displays structural as well as functional similarities to BRCA1 and is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Aberrant expression of TopBP1 may lead to genomic instability and can have pathological consequences. In this study we aimed to investigate expression of TopBP1 gene at mRNA and protein level in hereditary breast cancer. Real-time quantitative PCR was performed in 127 breast cancer samples. Expression of TopBP1 mRNA in lobular carcinoma was significantly lower compared with ductal carcinoma (p

Background DNA repair processes play an important role in protection against carcinogenic factors. Mutations in DNA repair genes, which code proteins engaged in repair processes, may lead to carcinogenesis and among others also to colorectal cancer (CRC) development. The genetic variability in RAD51 may contribute to the appearance and progression of various cancers including CRC. The aim of the study was to compare the distribution of genotypes of RAD51 135G>C and 172G>T polymorphism between colorectal cancer patients and controls. Material and methods Both polymorphisms were evaluated by PCR-RFLP methods in colorectal tissue of 320 colorectal cancer subjects and 320 healthy subjects who served as controls. Results In the present work we demonstrated a significant positive association between the RAD51 C/C genotype and colorectal carcinoma. Variant 135C allele of RAD51 increased the cancer risk. However, we did not observe any relationship between each polymorphism and colorectal cancer progression assessed by node metastasis, tumour size and Dukes' stage. Conclusions Our results suggest that variant genotypes of the 135G>C of RAD51 polymorphism may be positively associated with colorectal carcinoma in the Polish population. Further studies conducted on a larger group are required to clarify this point.

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.

Hereditary predisposition to breast cancer determined in large part by loss of function mutations in one of two genes BRCA1 and BRCA2. Besides BRCA1 and BRCA2 other genes are also likely to be involved in hereditary predisposition to breast cancer. TopBP1 protein is involved in DNA replication, DNA damage checkpoint response and transcriptional regulation. Expression of TopBP1 gene at the mRNA level was analyzed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 94 samples of hereditary breast cancer. Analysis of TopBP1 mRNA level showed that expression of TopBP1 is significantly downregulated in poorly differentiated breast cancer (grade III according Bloom-Richardson system (P

Background The main cause of chronic pancreatitis (CP) is excessive alcohol consumption. On the other hand, only 5–10% of heavy drinkers develop chronic pancreatitis. We have only limited information regarding the pathogenic mechanism by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have been mostly implicated in hereditary and idiopathic CP, but their presence in other types of this disease have also been reported. Aims The aim of the study was to determine the frequency of PRSS1 and SPINK1 mutations in patients with chronic alcoholic (ACP) and idiopathic pancreatitis (ICP) as well as to investigate their relation to the clinical course of the disease. Methods The study included 33 ACP and 14 ICP patients as well 46 healthy subjects. The diagnosis of CP was based on clinical data, ultrasound, and computed tomography. After isolation of DNA from peripheral blood two trypsinogen mutations were detected N29I and R122H by allelo-specific amplification polymerase chain reaction (ASA-PCR) and by the PCR-restriction fragment length polymorphism (RFLP). Beside this N34S mutation of SPINK1 was analyzed by PCR restriction fragment length polymorphism (PCR-RFLP). Results PRSS1 mutations have been detected in 11 (33%) patients with ACP. The frequency of the PRSS1 mutations was higher in patients with ACP than in controls (4.3%) (p

gene expression hadthe tendency to longer survival in all Dukes’ stages.Loss of mismatch repair (MMR) function is implicatedin the phenomena of microsatellite instability (MSI), whichis characterized by the accumulation of somatic alterationin the length of simple, repeated sequences; microsatellites(Ahmed 2003). MSI has been identified in tumours of hered-itary non-polyposis colorectal cancer (HNPCC) colorectalcancer and sporadic colorectal cancer, where it occurs in 10–15% of the cases (Gryfe

The aim of our study was to assess the clinical significance of -174G/C Il-6 gene polymorphism and Il-6 serum level in patients with pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The study included 41 with pancreatic adenocarcinoma, 56 with chronic pancreatitis, and 50 healthy volunteers, hospitalized between 2003 and 2006. Il-6 serum levels were measured with an enzyme-linked immunoassay and Il-6 gene polymorphism was studied in DNA isolated from peripheral blood. In PA and CP patients Il-6 serum levels were significantly higher than in the control group (P < 0.01). The levels of Il-6 in the patients with tumor size ≥3.5 cm were higher than that in patients with smaller tumors (P < 0.01). The elevated Il-6 levels were also correlated with the presence of liver metastases (P < 0.01). Mean Il-6 serum level was significantly higher in patients homozygous G/G for -174 Il-6 gene compared with patients with at least one C allele. Our findings indicate that -174G/C Il-6 gene polymorphism influences circulating Il-6 levels. Increased Il-6 serum levels may be correlated with tumor size and the presence of liver metastases in patients with pancreatic adenocarcinoma.

Recent studies suggest that genetic polymorphisms of the DNA repair genes have been implicated in breast cancer risk. BRCA1 and BRCA2, two breast cancer susceptibility genes, are essential to maintain chromosomal integrity. This is mediated via regulation of RAD51 during homologous recombination. Dinucleotide polymorphism repeats in the 15q14-21, 17q21 and 13q12-13 regions, where the RAD51, BRCA1 and BRCA2 genes are located, respectively, have been evaluated. The polymorphism was determined using the following microsatellite markers: D15S118, D15S214, D15S1006, D17S855, D17S1323, D13S260 and D13S290. Genotypes containing the (CA)(17) or (CA)(19) alleles in the RAD51 region were found to be associated with a decreased breast cancer risk. Genotype containing the (CA)(17) allele in the 13q12-13 region was found to be associated with an increased breast cancer risk. The results indicate that dinucleotide CA repeat polymorphism at RAD51 and BRCA2 gene regions might be associated with genetic susceptibility to breast cancer.

Background : Loss of heterozygosity (LOH) in the 15q14-21 and 13q12-13 regions can contribute to the inactivation of RAD51 and BRCA2 genes implicated in the pathogenesis of breast cancer. We investigated allelic losses in microsatellites in the RAD51 and BRCA2 regions, and their association with clinicopathological parameters in breast cancer. Methods : The LOH analysis was performed by amplifying DNA by PCR, using D15S118, D15S214, D15S1006 polymorphic markers in the 15q14-21 region and D13S260, D13S290 polymorphic markers in the 13q12-13 region in 36 sporadic breast cancer cases. Results : LOH in the RAD51 region ranged from 29% to 46% and in the BRCA2 region from 38% to 43% of informative cases. Eleven percent of the breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 44% of cases manifested statistically significant LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA2 regions. LOH in the RAD51 region similarly as in the BRCA2 region appeared to correlate with steroid receptors content and lymph node status. Discussion : The obtained results indicate that alteration in RAD51 region may contribute to the disturbances of DNA repair involving RAD51 and/or BRCA2 penetration and thus enhance the risk of breast cancer development.

Plasminogen activator inhibitor 1 (PAI-1) content in colorectal cancer tissue extracts may be of strong prognostic value: high levels of PAI-1 in tumours predict poor prognosis. The gene encoding PAI-1 is highly polymorphic and PAI-1 gene variability could contribute to the level of PAI-1 biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the 1334G/A polymorphism in 92 subjects with colorectal cancer in samples of cancer tissue and distant mucosa samples as well as in blood were investigated. Blood samples age matched healthy individuals (n = 110) served as control. The 1334G/A polymorphism was determined by PCR amplification using allele specific primers. No differences in the genotype distributions and allele frequencies between blood, distant mucosa samples and cancer tissue were detected. However, the distribution of the genotypes of the 1334G/A polymorphism in patients differed significantly (P < 0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the colorectal cancer subjects and controls (P < 0.05). The results support the hypothesis that the 1334G/A polymorphism may be associated with the incidence of colorectal cancer.

We analysed the distribution of genotypes of two polymorphisms in the urokinase-type plasminogen activator (uPA) gene: C→T substitution in exon 6 and T→C substitution in intron 7 in 52 subjects with colorectal cancer. Genotypes were determined in tumour tissue and distant mucosa samples by allele-specific polymerase chain reaction. The antigen levels of uPA in cancer tissue were higher than in distant mucosa as measured by enzyme-linked immunosorbent assay. The level of uPA antigens in cancer samples with the C/C genotype of C→T polymorphism in exon 6 was higher than in samples with C/T and T/T genotypes. No differences in the level of uPA antigens between the alleles of the intron 7 T→C polymorphism were found. As uPA can be involved in cancer invasion and metastasis, C/C genotype in exon 6 of uPA gene can be further considered as being related to colorectal cancer progression.

Esophageal adenocarcinoma (ADC) incidence has been increasing dramatically in the past 3 decades despite the surveillance programs in patients with Barrett’s esophagus (BE). Therefore, markers of early neoplastic progression are required to predict of cancer risk in BE patients. The aim of this study was to investigate the frequency of Her2/neu amplification in different stages during Barrett’s-related carcinogenesis.Her2/neu amplification analysis in 39 patients with gastroesophageal reflux disease (GERD), in 34 with BE, in 11 with dysplasia and 13 with ADC were performed with PCR.Her2/neu amplification was detected in 8% (3/39) GERD patients, 15% (5/34) with BE, 41% (7/17) with dysplasia and in 54% (7/13) with ADC. We observed an increasing trend in the frequency of Her2/neu alteration between BE-carcinogenesis stages (p=0.001). This finding was confirmed in the logistic regression analysis showing gradient in odds ratios between BE (2.07; 95% CI: 0.46-9.39), dysplasia (8.4; 95% CI: 1-83-38.53) and ADC (14.0; 95% CI: 2.81-69.69) compared to GERD; it was even higher after adjustment for age and gender.Her2/neu alterations may occur early and increasingly during Barrett’s malignant progression. We suggest that it may be useful to stratify the risk of adenocarcinoma in patients with Barrett’s esophagus.

Single nucleotide polymorphisms (SNPs) in DNA repair genes may be associated with differences in the repair efficiency of DNA damage and may influence an individual's risk of cancer. The XRCC3 protein plays a critical role in Homologous Recombination Repair (HRR) accounting for repair of DNA double-strand breaks (DSB).The aim of the present study was to evaluate associations between the risk of breast cancer and Thr241Met polymorphism in the XRCC3 gene.Single nucleotide polymorphism was genotyped by the PCR-RFLP (restriction fragment-length polymorphism) method in 760 women with sporadic breast cancer and in 760 control samples. The present study confirmed a relationship between XRCC3 Thr241Met polymorphism and breast cancer progression, assessed by the degree of lymph node metastases and histological stages.Our findings suggest that the analysis of XRCC3 polymorphism, may contribute to better understanding of the mechanisms of breast cancer by evaluating possible interactions between these genotypes and well-established risk factors for breast cancer.

The genes RAD51, XRCC2 and XRCC3 encode proteins that are important for the repair of double-strand DNA breaks by homologous recombination. Therefore, genetic variability in these genes may contribute to the occurrence and progression of endometrial cancer.The subject of investigation in the reported study was the distribution of genotypes and the prevalence of alleles of the RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphism in 230 cases of sporadic endometrial cancer; the polymorphisms were determined by polymerase chain reaction-restriction fragment-length polymorphism methods.The obtained results demonstrated a significant positive association between the RAD51 C/C genotype and endometrial carcinoma, with an adjusted odds ratio (OR) of 3.75 (P0.0001). The homozygous C/C genotype was found in 72% of endometrial cancer cases and in 19% of the used controls. The variant 135C allele of RAD51 increased the cancer risk (OR = 1.64 [1.28-2.10]P0.0001). There were no significant differences between the distribution of G135C, Arg188His and Thr241Met genotypes in the subgroups assigned to histological grades.The obtained results indicate that the polymorphism of RAD51, but not of either XRCC2 or XRCC3 genes, may be positively associated with the incidence of endometrial carcinoma in the population of Polish women. Further studies, including those on a larger group of patients, are required to further clarify this point.

Purpose Barrett's associated esophageal adenocarcinoma (ADC) is one of the malignancies of most rapidly increasing incidence. The aim of the study was to assess p16 tumor suppressor gene alterations in the ADC premalignant conditions. Material & Methods In the present study two p16 gene mutations (A148T and I49S) analysis with PCR- RFLP method have been performed in oesophageal biopsy specimen in 33 patients with Barrett's gastric metaplasia (GM), 27 - with Barrett's intestinal metaplasia (IM), 8 - with dysplasia and 11 - with ADC. Results We have detected the I49S mutation in 12% (4/33) patients with GM, 18% (5/27) with IM, 50% – with dysplasia (4/8) and in 27% (3/11) – with ADC. The A148T mutation were found in 3% (1/33) patients with GM, 22% (6/27) – IM, 25% (2/8) – dysplasia and 27% patients with ADC (3/11). The frequency of the A148S mutation was rising in GM – IM – dysplasia - ADC sequence and was significantly lower in GM compared to all other grades taken together (p=0.0256). The frequency of the I49S mutation was rising in GM – IM – dysplasia sequence, to drop in ADC cases. There were no significant differences in frequency of the I49S mutation between studied groups. Conclusions These findings are consistent with the hypothesis on the role of the p16 mutations in early phase of Barrett's epithelium progression to ADC. The presence of p16 mutations in esophageal metaplastic columnar epithelium without goblet cells suggest that this pathology may have malignancy potential.

The aim of this study was to investigate the cadmium (Cd), nickel (Ni) and aluminium (Al) concentrations in female breast cancer and normal tissue.The concentration of metals in 16 non-cancerous breast tissues and 67 breast cancer samples was measured by flame atomic absorption spectrometry.In the case of normal breast tissue the concentrations were 0.61 ± 0.24 μg Cd/g dry tissue, 1.84 ± 0.67 μg Ni/g dry tissue, and 3.63 ± 1.00 μg Al/g dry tissue, whereas in breast cancer concentrations of metals were 0.76 ± 0.38 μg/g dry tissue, 2.26 ± 0.79 μg/g dry tissue, and 4.40 ± 1.82 μg/g dry tissue, respectively. The concentration of Cd and Al in normal breast tissue was significantly lower than in breast cancer. In the case of Ni concentration, we did not observe statistically significant differences between normal and cancerous tissue. There were no significant differences in concentration of studied metals, in breast cancer, in the context of age, menopausal status, and cancer histological grading.The data obtained show higher concentration of cadmium and aluminium and support a possible relationship between those metals and breast cancer.

Despite advanced diagnostic and therapeutic procedures, endometrial cancer (EC) is still responsible for high morbidity and mortality of women. The genetic variability in RAD51 may contribute to the appearance and progression of various cancers including EC.We investigated the association of polymorphisms in the DNA repair genes RAD51 135GC and 172GT with endometrial cancer risk.The genotypes of RAD51 135GC and 172GT polymorphism were determined by PCR-RFLP methods in endometrial tissue of 240 cancer subjects and 240 healthy subjects who served as controls.In the present work we demonstrated a significant positive association between the RAD51 C/C genotype and endometrial carcinoma, with an adjusted odds ratio (OR) of 13.0 (p0.0001). The distribution of genotypes for 135GC SNP in endometrial cancer patients vs. controls was: 10% vs. 27% for GG, 13% vs. 58% for GC and 77% vs. 15% for CC genotype, respectively. Variant 135C allele of RAD51 increased the cancer risk (OR = 1.81; 95% CI 0.11-2.93, p = 0.022). The higher risk of EC occurrence was associated with the combined C135C-G172T genotype (OR = 7.69; 95% CI 3.45-17.12).The results indicated that the polymorphism 135GC of the RAD51 gene may be positively associated with endometrial carcinoma in the Polish population. Further studies, conducted on a larger group, are required to clarify this point.

Polymorphisms in the human oxoguanine glycosylase 1 ( hOGG1 ) and X-ray repair cross-complementing 1 ( XRCC1 ) genes have been extensively studied in the association with various human cancers such as endometrial cancer.The genotype analysis of hOGG1 Ser326Cys and XRCC1 Arg399Gln gene polymorphisms for 150 endometrial cancer patients and 150 controls of cancer-free subjects, in the Polish population, were performed using PCR-based restriction fragment length polymorphism (PCR-RFLP).Although there were no significant (p0.05) differences in the frequencies of genotypes or alleles of hOGG1 genes between patients and controls, the frequency of the XRCC1 399Gln allele was significantly greater in endometrial cancer patients compared with controls (p = 0.033) with an odds ratio of 1.39 (95% confidence interval 0.99 to 1.95). The distributions of genotypes and alleles of the genes hOGG1 and XRCC1 were not significantly associated with different grades of endometrial cancer (p0.05).In conclusion, these findings indicated that XRCC1 Arg399Gln polymorphism may be a genetic determinant for developing endometrial cancer. The hOGG1 Ser326Cys may not play an important role in susceptibility to endometrial cancer in Polish women.

Genetic polymorphisms in homologous recombination repair genes that can lead to protein haploinsufficiency are generally associated with increased cancer risk. The aim of the present study was to evaluate associations between the risk of breast cancer and single nucleotide polymorphisms in the genes, encoding three key proteins of the homologous recombination repair: RAD51 (the human homologue of the E. coli RecA protein), X-ray repair cross-complementing group (XRCC) 2 and XRCC3. The polymorphisms studied were G135C of the RAD51 gene (c. -98 G>C; rs1801320), Arg188His of the XRCC2 gene (c. 563 G>A; rs3218536), and Thr241Met of the XRCC3 gene (c. 722 C>T; rs861539). Each polymorphism was genotyped by the PCR-RFLP (restriction fragment-length polymorphism) method in 700 Polish female patients with sporadic breast cancer and in 708 cancer-free women, who served as controls. In the present study, we showed the association between RAD51 G135C polymorphism and the incidence of breast cancer (p < 0.0001), but found no significant association with XRCC2 Arg188His or XRCC3 Thr241Met polymorphism. Instead, significant association was identified between XRCC2 Arg188His or XRCC3 Thr241Met polymorphism and breast cancer progression, assessed by the histological grading. However, each of these three polymorphisms was not associated with the tumor size or the lymph node metastases. This study provides evidence that links single nucleotide polymorphisms of RAD51 and XRCC2/3 genes with the risk of breast cancer in Polish women. In conclusion, RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of sporadic breast cancer in female population.

Genetic polymorphism in XRCC1 and XRCC3 genes may influence DNA repair capacity and, in turn, confer predisposition to breast cancer.In the present work the distribution of genotypes and frequency of alleles of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Trp241 Met polymorphism in XRCC3 in breast cancer women were analysed. Blood samples were obtained from 150 women with breast cancer and controls (n = 106). The polymorphisms were determined by PCR-RFLP methods.No association between XRCC1 Arg399Gln and Arg194Trp genotype and breast cancer risk was observed. The distribution of the genotypes of the Trp241 Met polymorphism of XRCC3 in both controls and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage.The results suggest that the Arg194Trp and Arg399Gln polymorphism of the XRCC1 gene as well as Trp241 Met polymorphism in XRCC3 may not be linked with appearance and development of breast cancer.

The incidence of esophageal adenocarcinoma (ADC) has been increasing rapidly over the past few decades. Gastro-esopageal reflux disease (GERD), Barrett's esophagus (BE) and Barrett-associated dysplasia are a risk factor for esophageal cancer, but endoscopic surveillance have only a limited influence on cancer mortality. There is a great need to find molecular biomarkers predicting increased progression risk in GERD-Barrett's metaplasia-dysplasia-adenocarcinoma sequence to improve risk assessment and stratification of patients to surveillance program.To evaluate the polymorphism and prevalence of loss of heterozygosity (LOH) of APC tumor suppressor gene in mataplasia, dysplasia and adenocarcinoma.In esophageal mucosal samples of 79 patients with: GERD (n=33), BE (n=27), BE+dysplasia (n=8) and ADC (n=11) we have studied LOH of APC tumor suppressor gene using PCR-restriction fragment length polymorphism (RFLP). A 133 bp fragment, spanning exon 11 of the APC gene was amplified, and Rsal digestion of the PCR product defined the alleles as either homozygous 133 bp (Rsa(-/-)) or 87 and 46 bp (Rsa(+/+)) fragments, and heterozygous (Rsa(+/-)) exhibiting the three fragments. Control peripheral blood cell DNA samples have been collected from 60 normal healthy subjects.Among 79 patients, there were 16 heterozygous (20%) for APC gene. In 16 informative heterozygous LOH was detected in 7 cases: 2/5 with GERD, 3/7--with BE, 1/2--with BE+dysplasia and 1/2--with ADC. There were no statistical differences between studied groups (NS). Distribution of the three alleles, Rsa(+/-), Rsa(+/+), and Rsa(-/-) was: 38, 47 and 15% in the healthy individuals, 25%, 25% and 50%--in GERD patients, 29%, 41% and 29%--in BE, 36%, 45% and 18% in BE+dysplasia and 25%, 67% and 8% in ADC patients, respectively. The frequency of heterozygous cases in control group was significantly higher than in patients group (p = 0.018), whereas Rsa (-/-) were the most frequent in patients group (p = 0.008). Rsa (-/-) were seen significantly more often in GERD compared to ADC patients (p = 0.005), in opposite to Rsa (+/+), which were significantly more frequent in ADC vs. GERD (p = 0.007).APC gene inactivation concerns minority of patients with esophageal adenocarcinoma, however, its detection indicates higher risk of progression to ADC. APC alternations appear to be early in GERD-BE-dysplasia-ADC sequence. The specific polymorphism may identify patients with high risk of progression into BE.

CONTEXT AND OBJECTIVE: Estriol is an estrogen with considerably weaker stimulatory effects on endometrial proliferation than estradiol. A study was conducted to determine the level of estrogen receptors (ERs) and progesterone receptors (PRs) in women who received 14-day vaginal estriol therapy, compared with those who did not receive this therapy. ER and PR gene expression was analyzed in the endometrium, myometrium and vagina of postmenopausal women treated with estriol. DESIGN AND SETTING: Analytical cross-sectional study, at the Research Institute of the Polish Mothers' Memorial Hospital, Lodz, Poland. METHODS: Twenty-seven postmenopausal women (57-74 years of age) were included in the study. All of them were waiting for per vaginam hysterectomy or plastic surgery on the vagina and perineum because of uterine prolapse. ER and PR gene expression was determined by means of the technique of reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the estriol-treated patients, in comparison with the control group, a significant increase in ER gene expression was observed in the endometrium and vagina, while enhanced PR gene expression was found in the endometrium. However, under histological examination of the endometrium, estrogen stimulation of low and medium degree was diagnosed for 21.4% and 14.3% of the estriol-treated women, respectively. CONCLUSION: The results obtained suggest that the women who received 14 days of treatment with vaginal estriol had higher ER and PR mRNA levels. No difference between these groups regarding endometrial proliferation was observed.

Reduced DNA repair capacity can render a high risk of developing many types of cancer; including breast cancer. Polymorphisms in DNA repair genes may contribute the genetic instability and carcinogenesis. In the present work the distribution of genotypes and frequency of alleles of the Ser326Cys polymorphism of hOGG1 gene in breast cancer women were analysed. Blood samples were obtained from 100 women with breast cancer and control (n = 106). The polymorphism was determined by PCR-RFLP methods. No association between Ser326Cys polymorphism of hOGG1 and breast cancer risk was observed. The distribution of the genotypes of the Ser326Cys polymorphism in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the Ser326Cys polymorphism of hOGG1 gene may not be linked with appearance and development of breast cancer in polish women.

Estrogens play a crucial role in the pathogenesis and progression of breast and endometrial cancer. The gene ER-alpha is polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the Pvull polymorphism and Xbal polymorphism of ER-alpha gene in subjects with breast cancer were investigated.Blood samples were obtained from 103 postmenopausal women with breast cancer. The polymorphisms were determined by PCR-RFLP.The distribution of the genotypes of Pvull and Xbal polymorphism of ER-alpha in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage.The results suggest that the Pvull polymorphism of ER-alpha gene as well as Xbal polymorphism may not be linked with appearance and development of breast cancer.

Common polymorphism in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. In present work we investigated the association between XPD Lys751Gln polymorphism and breast cancer progression. The polymorphism was analysed in breast cancer patients (n = 92) in blood. Blood samples from age matched healthy women served as control (n = 110). XPD genotypes were measured by PCR-RFLP. The distribution of the genotypes of the Lys751Gln polymorphism in patients differed significantly (p0.05) from those predicted by the Hardy-Weinberg equilibrium. There were significant differences in the frequencies of alleles between the breast cancer subjects and controls (p0.05). The results support the hypothesis that the Lys751Gln polymorphism of XPD gene may be associated with the incidence of breast cancer.

Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency may therefore be associated with cancer risk.In the present work the distribution of genotypes and frequency of alleles of the Lys751Gln polymorphism of XPD gene in subjects with breast cancer were investigated.Genomic DNA isolated from 92 breast cancer patients and control (n=110) was used to genotype XPD Lys751Gln by means of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.The distribution of the genotypes of the Lys751Gln polymorphism of XPD in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage.The results suggest that the Lys751Gln polymorphism of XPD gene may not be linked with appearance and development of breast cancer.

Women with high circulating estrogens concentration have increase risk of breast, endometrium and ovarian cancer, thus it is important to identify factors, including environmental and genetic variability that may be alter estrogen concentration.In the present work the distribution of genotypes and frequencies of alleles of the T/C polymorphism of CYP19 and G/A polymorphism of COMT gene in subjects with endometrial cancer were investigated. Paraffin embedded tumour tissues was obtained from 151 postmenopausal women with endometrial cancer. The polymorphism's were determined by PCR-RFLP methods.The distribution of the genotypes of the T/C and G/A polymorphism in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. Additionally, there were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage.The results suggest that the CYP19 and COMT polymorphism may not be linked with appearance and development of endometrial cancer but further research, conducted on larger population, are needed to clarify this point.

Common polymorphism in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis.In the present work the distribution of genotypes and frequency of alleles of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Arg415Gln polymorphism in ERCC4/XPF in subjects with breast cancer were investigated.Blood samples were obtained from 100 women with breast cancer and control (n = 106). The polymorphisms were determined by PCR-RFLP.The distribution of the genotypes of the Arg194Trp and Arg399Gln polymorphism of XRCC1 and Arg415Gln polymorphism of ERCC4/XPF 9 in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage.The results suggest that the Arg194Trp andArg399Gln polymorphism of XRCC1 gene as well as Arg415Gln polymorphism in ERCC4/XPF may not be linked with appearance and development of breast cancer.

This study was carried out to evaluate the loss of heterozygosity (LOH) in the 8q12-q24.1 chromosomal region, containing RAD54B gene in breast cancer. Polymorphic markers D8S539 and D8S543 were used. For alleles frequency estimation 100 primary breast cancers were tested. DNA was isolated from paraffin-embedded tissues and their matched blood samples. Polymerase chain reaction amplified products of normal and tumor DNA pairs were compared in ABI PRISM 377 DNA sequencer. In analyzed cases LOH was found in 1% and 2% of informative cases for microsatellite markers D8S539 and D8S543, respectively. This date indicate, that LOH isn't predictive for breast cancer.

RAD51, RAD52, and RAD54 encode proteins that are critical to the repair of double-strand DNA breaks by homologous recombination. The objectives of this study were to determine the frequency of BRCA1 germ-line mutations and the RAD52, RAD54 and RAD54B microsatellite instability (MSI) and loss of heterozygosity (LOH) in patients with breast cancer.Blood and tumour tissue were obtained from 100 breast cancer women. Blood samples age matched healthy individuals (n = 60) served as control.The microsatellite instability status was significantly higher in breast cancer tissue compared as control (p0.05). Significant correlation between one or more regions with concomitant LOH and pathologic parameters were observed with respect to progesterone receptors (p = 0.004) and tumour grade (p = 0.001). In present study one Ex20insC and two ExII17delA mutations of BRCA1 gene were identified in women with breast cancer.The results suggest that the microsatellite instability and LOH seems to be important in the development sporadic breast cancer. The lack of detectable BRCA1 germ-line mutations in most cases suggests that there are probably additional, as yet unidentified genes predisposing to this disease.

The development of breast cancer is associated with an accumulation of specific genetic alterations. These genetic changes affect malignant transformation of both dysregulation of cell proliferation and apoptosis. Apoptotic cell death is a frequent phenomenon in breast cancer. In present work we investigated the association between apoptosis and breast cancer progression. The apoptosis was analysed in breast cancer patients (n=103) in blood and tumour specimens. Blood samples from age matched healthy women served as control (n=90). The apoptosis was detected by special staining techniques TUNEL and by agarose gel electrophoresis. The apoptotic cells were identified in 69.9% (72/103) of the breast cancers and in 1.1% control (1/90). The number of positive samples were significantly higher among cancer samples than among control samples (P0.001). There were the significant difference in terminal deoxynucleotide transferase-mediated deoxyuridine triphisphate-biotin nick end-labelling index between ductal breast carcinoma and the other histological types. Sex steroid recepor negative tumors have greater apoptotic index than the sex steroid receptor positive ones. The high frequency of apoptotic cells in breast tumours suggests a potential role of apoptosis in cancer appearance and/or progression.

Mutations in the MMAC/PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene are documented in cancers of the breast, prostate, ovary, colon, melanoma, glioblastoma, lymphoma and endometrium. In the present work MMAC/PTEN gene expression in women with endometrial adenocarcinoma (n=70) in RNA samples obtained from cancer tissue were investigated. Control DNA was obtained from 68 normal endometrial tissue. The MMAC/PTEN expression was determined by RT-PCR analysis. The expression of MMAC/PTEN gene in endometrial adenocarcinoma cases was significantly reduced compared to the expression in the normal samples (P0.05). Furthermore the significant difference (P0.05) was observed between the expression of MMAC/PTEN in stage III versus lower stages of endometrial cancer. The results support the hypothesis that the MMAC/PTEN gene expression may be associated with the incidence of endometrial cancer.

Breast cancer is the most prevalent cancer type in women. Accumulating evidence indicates that the fidelity of double-strand break repair in response to DNA damage is an important step in mammary neoplasias. The RAD51 and BRCA1 proteins are involved in the repair of double-strand DNA breaks by homologous recombination. In this study, we evaluated loss of heterozygosity (LOH) in the RAD51 and BRCA1 regions, and their association with breast cancer. The polymorphic markers D15S118, D15S214 and D15S1006 were the focus for RAD51, and D17S855 and D17S1323 for BRCA1. Genomic deletion detected by allelic loss varied according to the regions tested, and ranged from 29 to 46% of informative cases for the RAD51 region and from 38 to 42% of informative cases for the BRCA1 region. 25% of breast cancer cases displayed LOH for at least one studied marker in the RAD51 region exclusively. On the other hand, 31% of breast cancer cases manifested LOH for at least one microsatellite marker concomitantly in the RAD51 and BRCA1 regions. LOH in the RAD51 region, similarly as in the BRCA1 region, appeared to correlate with steroid receptor status. The obtained results indicate that alteration in the RAD51 region may contribute to the disturbances of DNA repair involving RAD51 and BRCA1 and thus enhance the risk of breast cancer development.

The development of breast cancer is associated with an accumulation of specific genetic alterations. The aim. In this study the distribution of G/G, G/C and C/C genotype and frequencies of the G and C allele of RAD51 G/C polymorphism in women with breast cancer was examined.85 breast cancer samples were included in this study. They were categorised according to Scarf-Bloom-Richardson criteria in women with breast cancer. Blood samples age matched healthy individuals (n = 91) served as control.The distribution of the genotypes of the G/C polymorphism RAD51 in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences in the genotype distributions and allele frequencies between node-positive and node-negative patients.Our study implies that it is possible that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer but further researches, conducted on larger population, are needed to clarify this point.

Microsatellite instability (MSI) is due to defective DNA mismatch repair and is characteristic of HNPCC tumours.The role of MSI in familial predisposition to colorectal cancer was investigated in this study by microsatellite analysis among familial cases.PCR-based microsatellite analysis was performed in blood obtained from 30 members from HNPCC families. Blood samples age matched healthy individuals (n = 28) served as control. MSI was studied at five loci containing single- or dinucleotide repeat sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12), BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12).MSI frequency was higher in member of HNPCC families (40%) than in control (10.7%) cases. Out of the 30 samples tested, 12 were found to be MSI positive, 9 MSI high and 3 MSI low.The present study suggest that microsatellite instability seem to be a risk factor of colorectal cancer in subjects belonged to HNPCC families with high incidence of this cancer.

Endogenous estrogen exposure is an important determinant of endometrial cancer risk. The CYP 17 and CYP 19 genes encode 17alphahydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. The genes CYP17 and CYP19 are polymorphic and gene variability could contribute to the level of protein biosynthesis. In the present work the distribution of genotypes and frequency of alleles of the C/T polymorphism in promoter region of CYP17 and G/A polymorphism at position Val80 in CYP19 in subjects with endometrial cancer were investigated. Paraffin embedded tumor tissues were obtained from 100 women with endometrial cancer. DNA from normal endometrial tissue (n=106) served as control. The polymorphisms were determined by PCR-RFLP. The distribution of the genotypes of the C/T polymorphism of CYP17 and G/A polymorphism of CYP19 in both control and patients did not differ significantly (p0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the C/T polymorphism of CYP17 gene as well as G/A polymorphism of CYP19 may not be linked with appearance and development of endometrial cancer.

Breast cancer is a significant cause of morbidity and mortality in Western countries. In the present work the distribution of genotypes and frequency of alleles of the RAD51 G/C polymorphism and the frequency of BRCA1 germ-line mutations in patients with breast cancer were investigated. One hundred breast cancer women provided blood for mutation analysis. Blood samples from age matched healthy individuals (n=106) served as control. The G/C polymorphism and BRCA1 mutations were determined by PCR-RFLP methods. The distribution of the genotypes of the G/C polymorphism RAD51 in both control and patients did not differ significantly (P0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences in the genotype distributions and allele frequencies between node-positive and node-negative patients. In the present study one Ex20insC mutation of BRCA1 gene was identified in women with breast cancer. Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer. The lack of detectable BRCA1 germ-line mutations in most cases suggests that there are probably additional, as yet unidentified genes predisposing to this disease.

BRCA1 tumor suppressor gene encodes an 1863-amino acid gene product that is implicated in many cellular pathways including transcription, cell-cycle checkpoint control, apoptosis and DNA repair. A role of apoptosis and BRCA1 germ-line mutation in breast cancer appearance was investigated in this study by both apoptosis frequency analysis and mutation screening of BRCA1 among breast cancer cases. Blood was obtained from 40 women with node-negative and node-positive ductal breast carcinomas with uniform tumor size. The blood samples from age matched healthy women (n=42) served as control. BRCA1 gene mutations were determined by PCR-RFLP methods. The apoptotic peripheral blood cells were detected by agarose gel electrophoresis. The apoptotic cells were identified in 30% (12/40) of the patients. There were no significant differences in apoptosis frequencies between patients and controls (P0.05). Three mutations of BRCA1 gene were identified in apoptosis positive samples from breast cancer women; one Ex20insC and two ExII17delA. Our study implies that apoptosis may be involved not only in sporadic breast carcinoma without BRCA1 mutations, but also in BRCA1-associated breast carcinoma.