Production and characterization of rhamnolipids by Pseudomonas aeruginosa isolated in the Amazon region, and potential antiviral, antitumor, and antimicrobial activity.

Biosurfactants encompass structurally and chemically diverse molecules with surface active properties, and a broad industrial deployment, including pharmaceuticals. The interest is growing mainly for the low toxicity, biodegradability, and production from renewable sources. In this work, the optimized biosurfactant production by Pseudomonas aeruginosa BM02, isolated from the soil of a mining area in the Brazilian Amazon region was assessed, in addition to its antiviral, antitumor, and antimicrobial activities. The optimal conditions for biosurfactant production were determined using a factorial design, which showed the best yield (2.28 mg/mL) at 25 °C, pH 5, and 1% glycerol. The biosurfactant obtained was characterized as a mixture of rhamnolipids with virucidal properties against Herpes Simplex Virus, Coronavirus, and Respiratory Syncytial Virus, in addition to antimicrobial properties against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecium), at 50 µg/mL. The antitumor activity of BS (12.5 µg/mL) was also demonstrated, with potential selectivity in reducing the proliferation of breast tumor cells, after 1 min of exposure. These results demonstrate the importance of studying the interconnection between cultivation conditions and properties of industrially important compounds, such as rhamnolipid-type biosurfactant from P. aeruginosa BM02, a promising and sustainable alternative in the development of new antiviral, antitumor, and antimicrobial prototypes.

Expression of Ki67 and p53 Proteins: Breast Cancer Aggressivity Markers in Brazilian Young Patients.

Background: The increase in breast cancer (BC) cases in young women is of great importance since the tumor behavior in this group is generally more aggressive than in their older counterparts, and strategies for early diagnosis and prognostication are needed. Therefore, this work sought to investigate prognostic markers associated with young (<44 years old) BC patients. Methods: Two hundred thirty-six primary tumor tissues from 232 BC patients, of which 44 had less than 44 years at diagnosis were evaluated regarding the expression of estrogen and progesterone receptors (ER and PR), human epidermal growth factor receptor 2 (HER2), Ki67, and p53 (used as an indicator of p53 mutations) through immunohistochemistry. Also, data regarding tumor size, histopathological grade (HG), lymph node metastasis disease stage, and patients' survival status were collected. Results: Early age tumors had higher Ki67 expression and p53 mutations, and these markers were positively correlated with each other and associated worse prognosis parameters, such as negativity for ER and PR and positivity for HER2, and with higher HG, tumor size, and disease stage. In young patients, Ki67 correlated with ER, PR, and HG, whereas p53 correlated with HER2 and disease stage. Also, Ki67 associated with BC death independently of time from diagnosis, patients age, tumor size, and disease stage, and showed a trend toward a positive correlation with death in young patients, but not in the older group. Conclusion: Young BC patients were more likely to have intensely proliferative tumors with p53 mutations and these markers may hold prognostic relevance in BC, especially in this subgroup of patients.

Germline APOBEC3B deletion influences clinicopathological parameters in luminal-A breast cancer: evidences from a southern Brazilian cohort.

PURPOSE: APOBEC3A and APOBEC3B cytidine deaminases have been implicated in the pathogenesis of multiple cancers, including breast cancer (BC). A germline deletion linking APOBEC3A and APOBEC3B loci (A3A/B) has been associated with higher APOBEC-mediated mutational burden, but its association with BC risk have been controversial. Therefore, this study investigated the association between A3A/B and BC susceptibility and clinical presentation in a Brazilian cohort. METHODS: A3A/B deletion was evaluated through allele-specific PCR in 341 BC patients and 397 women without familial or personal history of neoplasia from Brazil and associations with susceptibility to BC subtypes were tested through age-adjusted logistic models while correlations with clinicopathological parameters were tested using Kendall's tests. RESULTS: No association was found between A3A/B and BC susceptibility; however, in Luminal-A BCs, it was positively correlated with tumor size (Tau-c = 0.125) and Ki67 (Tau-c = 0.116) and negatively correlated with lymph node metastasis (LNM) (Tau-c = - 0.162). The negative association between A3A/B with LNM in Luminal-A BCs remained significant even after adjusting for tumor size and Ki67 in logistic models (OR = 0.22; p = 0.008). CONCLUSION: These results show that although A3A/B may not modify BC susceptibility in Brazilian population, it may affect clinicopathological features in BC subtypes, promoting tumor cell proliferation while being negatively associated with LNM in Luminal-A BCs.

Transforming growth factor beta receptor II (TGFBR2) promoter region polymorphism in Brazilian breast cancer patients: association with susceptibility, clinicopathological features, and interaction with TGFB1 haplotypes.

PURPOSE: Transforming growth factor beta (TGFß) has paradoxical effects in breast cancer (BC), inhibiting initial tumors while promoting aggressive ones. A polymorphism on TGFBR2 promoter region (G-875A, rs3087465) increases TGFß type II receptor expression and is protective against cancer. Previously, we have shown that TGFB1 variants have subtype-specific roles in BC. This work sought to investigate the association between TGFBR2 and susceptibility and clinicopathological features in BC subgroups. METHODS: TGFBR2 G-875A was analyzed through PCR-RFLP in 388 BC patients and 405 neoplasia-free women. Case-control analyses as well as interaction with TGFB1 haplotypes previously associated with BC were tested through age-adjusted logistic regression. Correlations between G-875A and clinicopathological parameters were assessed through Kendall's Tau-b test. All statistical tests were two-tailed (α = 0.05). RESULTS: TGFBR2 G-875A was protective against BC in additive, genotypic, and dominant models. In subgroup-stratified analyses, these effects were greater in hormonal receptor-positive and luminal-A tumors, but were not significant in other subgroups. Logistic models including TGFB1 variants showed that in luminal-A tumors, G-875A retained its significance while TGFB1 haplotype showed a trend towards significance; otherwise, in HER2+ tumors TGFB1 variants remained significant while TGFBR2 showed a trend for association. There was no interaction between these genes. In correlation analyses, G-875A positively correlated with histopathological grade in total sample, and a trend towards significance was observed in triple-negative BCs. CONCLUSION: These results indicate that G-875A is a protective factor against BC, especially from luminal-A subtype, but may promote anaplasia in established tumors, consistent with TGFß signaling roles in BC.

HER2 Ile655Val polymorphism is negatively associated with breast cancer susceptibility.

BACKGROUND: The HER2 (human epidermal growth factor receptor-2) Ile655Val (rs1136201) genetic polymorphism can alter the receptor structure and its auto-activation, which can modify the signal transduction and, consequently, the cell cycle regulation. For this reason, this polymorphism has been extensively investigated as a candidate marker for breast cancer (BC). In this context, the aim of this study was to evaluate the possible influence of HER2 Ile655Val in BC susceptibility and prognostic factors in a Brazilian population. METHODS: Polymorphism genotype was assessed through RFLP-PCR in 107 BC patients with clinicopathological data available and in 150 women with no evidence of neoplasia and with no familial history of BC as control group. Association between this polymorphism and BC susceptibility and clinical parameters was evaluated through odds ratio (OR) and chi-squared or Fisher's exact test, respectively. RESULTS: A significant negative association between valine allele and BC susceptibility in dominant model was found (OR 0.5; 95% CI 0.27-0.93, P = .036). No significant association was found in relation to BC clinicopathological features (tumor size, lymph nodes commitment, histological grade, HER2 overexpression, hormonal receptors, p53, and Ki-67). CONCLUSION: Although this polymorphism did not demonstrate potential as a prognostic marker, it may be a suitable susceptibility marker for BC.

Interleukin 7 receptor alpha Thr244Ile genetic polymorphism is associated with susceptibility and prognostic markers in breast cancer subgroups.

Interleukin-7 (IL-7) exerts crucial functions on lymphoid cells' development and maintenance. In breast cancer (BC), IL-7 promotes growth of tumor cells in culture through the activation of JAK1/3-STAT5 and PI3K/AKT pathways, and expression of IL-7 signaling components was associated with worst prognosis. AC>T polymorphism (rs6897932; Thr244Ile) at exon 6 of IL-7 receptor alpha (IL-7Rα) gene (IL7RA) shifts the balance between the membrane-bound and soluble IL-7Rα splicing variants and was previously associated with autoimmune diseases, but has not been studied in cancer, including BC, so far. Therefore, the present study aimed to investigate the possible association of this polymorphism with the susceptibility and clinicopathological parameters of BC subgroups. IL7RA Thr244Ile was genotyped through PCR-RFLP in 403 women without neoplasia, no personal history of malignancy or family history of BC and in 338 BC patients with clinicopathological data available. BC patients were stratified according to their positivity for estrogen (ER) and/or progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Age-adjusted logistic regression was performed for case-control analyses, and correlations with clinicopathological parameters were assessed through Kendall's Tau-b coefficient. All analyses were two-tailed and had 95% confidence interval. In ER-PR-HER2- BCs, TT genotype was associated with increased susceptibility both in genotypic (TT vs. CC: OR=3.07; CI=1.01-9.38; p=0.05) and recessive (TT vs. CC+CT: OR=3.59; CI=1.19-10.85; p=0.02) models and negatively correlated with disease stage (Tau-b=-0.27; p=0.05). Whereas T allele was positively correlated with histopathological grade (Tau-b=0.29; p=0.03) and lymph node metastasis (Tau-b=0.35; p=0.02) in ER/PR+HER2+BCs and with Ki67 (Tau-b=0.51; p=0.008) in ER-PR-HER2+ subgroup. These data indicate that IL-7Rα is involved in BC, and that IL7RA polymorphism may play distinct roles in breast carcinogenesis according to BC subtype, pointing this genetic variant as an interesting marker for breast carcinogenesis to be validated by further mechanistic and prospective studies with larger samples.

The prognostic value of regulatory T cells infiltration in HER2-enriched breast cancer microenvironment.

Breast cancer represents a complex and heterogeneous disease that comprises distinct disease conditions, histological features, and clinical outcome. Since many years, it has been demonstrated as an association between HER2 amplification and poor prognosis, because its overexpression is associated with an aggressive phenotype of breast tumor cells. A significant proportion of cases have developed resistance to the current therapies available. Consequently, new prognostic markers are urgently needed to identify patients who are at the highest risk for developing metastases. During the past decade, new insights provided valuable knowledge regarding mechanisms underlying the dynamic interplayed between immune cells and tumor progression. It has been shown that the presence of a lymphocytic infiltrate, particularly of regulatory T cells, in cancer tissue, is associated with clinical outcome promoting rather than inhibiting cancer development and progression. It has been also verified that the clinical value of lymphocytic infiltration in breast cancers could be subtype-dependent, including the HER2-enriched subtype. In this context, this work summarizes proposed to discuss the prognostic value of regulatory T cell infiltration in microenvironment of HER2-enriched breast cancer.

Glutathione S-transferases deletions may act as prognosis and therapeutic markers in breast cancer.

Breast cancer (BC) is the main worldwide neoplasia in women. The metabolic balance between xenobiotic absorption and elimination rates plays an important role in preventing DNA damage and, consequently, tumor development. The glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the NAD(P)H quinone oxidoreductase are important enzymes involved in phase II detoxification reactions. Deletions in GSTM1 and GSTT1, and single-nucleotide polymorphism (SNP) in NQO1 (rs1800655) have been investigated in cancer context, revealing conflicting results. The present study analyzed these genetic polymorphisms in 121 BC patients and 151 BC-free controls in order to verify if they could act as susceptibility modifiers and/or prognostic factors. Binary logistic regressions adjusted by age were performed to assess associations between allelic variants and interactions in polymorphisms combination with BC susceptibility, but no significant association was found. Genotypes distribution was also compared between BC subtypes, but no significant difference was observed (p > 0.05). GSTM1 deletion was significantly associated with histopathological grade, with a greater proportion of patients presenting grade III tumors (p = 0.007). Univariate analysis identified tumor size as the only clinicopathological parameter potentially associated with recurrence risk in patients that received adjuvant chemotherapy (p < 0.1). Thus, logistic regression analysis adjusted by tumor size revealed a positive association between GSTT1 deletion and recurrence risk in general BC (OR 4.25; p = 0.04), while GSTM1 was negatively associated with recurrence risk in ER/PR+HER2- samples (OR 0.07; p = 0.03). In conclusion, the present study indicated that GSTT1 deletion was associated with increased recurrence risk, while GSTM1 correlated with worst prognosis parameters at diagnosis, but was negatively associated with recurrence risk in luminal subtype samples.

FOXP3 Allelic Variants and Haplotype Structures Are Associated with Aggressive Breast Cancer Subtypes.

FOXP3 genetic polymorphisms have been associated with cancer development and prognosis. In this context, the present study aimed to evaluate the g.10403A>G (rs2232365) polymorphisms and g.8048A>C (rs3761548), in aggressive breast cancer (BC) subtypes, including, Luminal B HER2+ (LB), HER2-enriched (HER2+), and triple-negative (TN). Polymerase chain reaction followed by enzymatic restriction was performed to genotyping 117 BC samples and 300 controls. A significant association of AA genotype (g.10403A>G) in relation to BC susceptibility (OR = 1.93; 95% CI = 1.01-3.66; p = 0.046) was observed. The GG (g.10403A>G) genotype was correlated with higher proliferation index (Ki-67) in HER2+ subtype (τ = 0.47; p = 0.019) and advanced TNM staging in TN (τ = 0.23; p = 0.032). A correlation of AA genotype (g.8048A>C) with higher Ki-67 (τ = -0.47; p = 0.018) and lower histological grade (τ = 0.39; p = 0.026) in HER2+ was also found. GA haplotype was correlated with lower histological grade (τ = -0.15; p = 0.009) and higher Ki-67 (τ = 0.43; p = 0.036) in HER2+ and advanced staging in TN (τ = 0.29; p = 0.044). On the other hand, AC haplotype was correlated with lower Ki-67 (τ = -0.54; p = 0.005) and staging (τ = -0.29; p = 0.027) in HER2+ and TN respectively. Results showed that FOXP3 influence regarding clinical outcome depends greatly on the BC subtype and indicated this transcription factor as a promising marker in aggressive BC subtypes.

Wilms' tumor susceptibility: possible involvement of FOXP3 and CXCL12 genes.

BACKGROUND: Wilms' tumor is an embryonal neoplasm of the kidney that accounts for approximately 6 % of all childhood tumors. The chemokine CXCL12 (C-X-C chemokine ligand 12) and its ligand CXCR4 (C-X-C chemokine receptor type 4) are involved in the development of several organs, including the kidney, and are also associated with tumor growth and metastasis. FOXP3 (forkhead transcription factor 3) was initially described as a marker for regulatory T cells; however, its expression in several types of tumor cells has already been described and may have prognostic significance. The aim of the present study was to analyze rs3761548 and rs2232365 FOXP3 polymorphisms, as well as evaluate rs1801157 CXCL12 polymorphism in Wilms' tumor samples. METHODS: Polymorphisms were evaluated in 32 patients and 78 neoplasia-free controls. Genotypes of rs1801157 were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) method, and genotypes of rs2232365 and rs3761548 were determined using allele-specific PCR (AS-PCR). RESULTS: The case-control study indicated a significant association for allele A carriers of rs1801157 polymorphism in relation to Wilms' tumor susceptibility (OR = 5.261; 95 % CI 2.156 to 12.84; p = 0.0002). The opposite was observed in male carriers of G allele for rs2232365 polymorphism (OR 0.1164; 95 % CI 0.0227 to 0.5954; p = 0.0091) or when male and female subjects were analyzed (OR = 0.1304; 95 % CI 0.05013 to 0.3394; p < 0.0001). CONCLUSIONS: All in all, these markers may contribute to this neoplasia susceptibility and progression; however, further studies are needed to real clarify their role in Wilms' tumor pathogenesis.

CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.

Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation.

Genetic Polymorphism and Expression of CXCR4 in Breast Cancer.

CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p = 0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p = 0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p < 0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis.

Immunohistochemical expression of CXCR4 on breast cancer and its clinical significance.

Many tumor cells express chemokines and chemokine receptors, and, for this reason, these molecules can affect the tumor progression. It is known that breast cancer is a complex and heterogeneous neoplasia comprising distinct diseases, histological characteristics, and clinical outcomes. The most studied role for CXCL12 chemokine and its receptor CXCR4 in breast cancer pathogenesis is the metastasis event, although several reports have demonstrated its involvement in other processes, such as angiogenesis and tumor growth. It has been found that CXCR4 is required for breast cancer cell migration to other sites such as lung, bone, and lymph nodes, which express high levels of CXCL12 chemokine. Therefore, CXCR4 is being considered a prognostic marker in breast cancer. Within this context, this review summarizes established studies involving expression of CXCR4 on breast cancer, focusing on its clinical significance.

Absence of Association between CCR5 rs333 Polymorphism and Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. Ordinarily, these cells express CCR5 chemokine receptor, which directs the immune response to a cellular pattern and is involved in cancer pathobiology. The genetic rs333 polymorphism of CCR5 (Δ32), results in a diminished receptor expression, thus leading to impaired cell trafficking. The objective of the present study was to investigate the effect of CCR5 chemokine receptor rs333 polymorphism in the pathogenesis of ALL. The genotype distribution was studied in 79 patients and compared with 80 control subjects, in a childhood population of Southern Brazil. Genotyping was performed using DNA samples amplified by polymerase chain reaction with sequence-specific primers (PCR-SSP). The homozygous (Δ32/Δ32) deletion was not observed in any subject involved in the study. Heterozygous genotype was not associated with ALL risk (OR 0.7%; 95% CI 0.21-2.32; P > 0.05), nor recurrence status of ALL (OR 0.86; 95% CI 0.13-5.48; P > 0.05). This work demonstrated, for the first time, no significant differences in the frequency of the CCR5/Δ32 genotype between ALL and control groups, indicating no effect of this genetic variant on the ALL susceptibility and recurrence risk.

CC chemokine receptor 5: the interface of host immunity and cancer.

Solid tumors are embedded in a stromal microenvironment consisting of immune cells, such as macrophages and lymphocytes, as well as nonimmune cells, such as endothelial cells and fibroblasts. Chemokines are a type of small secreted chemotactic cytokine and together with their receptors play key roles in the immune defense. Critically, they regulate cancer cellular migration and also contribute to their proliferation and survival. The CCR5 chemokine receptor is involved in leucocytes chemotaxis to sites of inflammation and plays an important role in the macrophages, T cells, and monocytes recruitment. Additionally, CCR5 may have an indirect effect on cancer progression by controlling the antitumor immune response, since it has been demonstrated that its expression could promote tumor growth and contribute to tumor metastasis, in different types of malignant tumors. Furthermore, it was demonstrated that a CCR5 antagonist may inhibit tumor growth, consisting of a possible therapeutic target. In this context, the present review focuses on the establishment of CCR5 within the interface of host immunity, tumor microenvironment, and its potential as a targeting to immunotherapy.

Molecular markers for breast cancer: prediction on tumor behavior.

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence.

BACKGROUND: Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. MATERIALS AND METHODS: Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. RESULTS: Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05-4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24-9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95-23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23-129.91, P<0.006). CONCLUSION: This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress.

Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients.

BACKGROUND: The capacity for DNA repair is essential in maintaining cellular functions and homeostasis; however, this capacity can be altered based on DNA sequence variations in DNA repair genes, which may contribute to the onset of cancer. Many single-nucleotide polymorphisms (SNPs) in repair genes have been found to be associated with oral cancer. The aim of this study was to investigate the relationship between the presence of allelic variants Arg194Trp (rs:1799782) and Arg399Gln (rs: 25487) of XRCC1 gene and Thr241Met (rs: 861539) of XRCC3 gene and susceptibility to oral cancer. We also attempted to correlate the frequencies obtained for each of the SNPs to histopathological parameters. METHODS: A case-control study was conducted with genomic DNA from 150 patients with oral squamous cell carcinomas and 150 controls. SNPs were genotyped by RFLP-PCR. RESULTS: The presence of the polymorphic variants of the XRCC1 gene within codon 194 (OR 0.82, 95% CI: 0.44-1.51) and codon 399 (OR 0.94, 95% CI: 0.59-1.50) and within the XRCC3 gene (OR 0.72; 95% CI: 0.45-1.16) were not associated with an increased risk of oral cancer. A combinational analysis of SNPs in both genes indicated no association. The presence of the allelic variants of these two genes had no statistically significant effect on tumor differentiation, lymph node invasion or tumor size. CONCLUSIONS: These results suggest that allelic variants of XRCC1 and XRCC3 are not suitable markers for susceptibility to carcinomas of the oral cavity and are also not related to the later stages of such tumors.

Evaluation of the influence of polymorphic variants CYP1A1 2B, CYP1B1 2, CYP3A4 1B, GSTM1 0, and GSTT1 0 in prostate cancer.

BACKGROUND/OBJECTIVE: Genetic polymorphisms in cytochrome P-450 (CYPs) and glutathione S-transferase (GSTs) genes can influence the appearance of tumors by the formation of new enzymes with altered activities. In the present study, 5 polymorphic variants were examined in 154 patients with prostate carcinoma and in 154 controls. MATERIALS AND METHODS: DNA analysis was carried out through PCR-based methods. The statistical methods used were odds ratio and confidence interval (95% CI), χ(2), Fisher, and Mann-Whitney. RESULTS: The study showed absence of association for CYP1A1 2B, CYP1B1 2, GSTM1 0, and GSTT1 0. The statistical analysis implied a positive association of variant CYP3A4 1B for prostate cancer. The combined analysis of CYP1A1 2B, CYP1B1 2, and CYP3A4 1B genotypes showed positive association. The analysis of histopathologic parameters detected statistically significant differences for Gleason score and biochemistry recurrence risk. The presence of the GSTT1 0 genotype in red meat consumers increased the risk for this disease. CONCLUSION: Some polymorphic variants analyzed can influence the development and the progression of prostate cancer.