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ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3'UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05-5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03-4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39-19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.
Molecular Biology Reports 05/2013; · 2.93 Impact Factor
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ABSTRACT: The FOXP3 gene encodes a transcription factor thought to be important for the development and function of regulatory T cells (Treg cells). These cells are involved in the regulation of T cell activation and therefore are essential for normal immune homeostasis. Signals from microenvironment have a profound influence on the maintenance or progression of diseases. Thus, Tregs have an important marker protein, FOXP3, though it does not necessarily confer a Treg phenotype when expressed. FOXP3 polymorphisms that occur with high frequency in the general populations have been studied in common multifactorial human diseases. Dysfunction of FOXP3 gene product could result in lack of Treg cells and subsequently chronically activated CD4+ T cells which express increased levels of several activation markers and cytokines, resulting in some autoimmune diseases. In contrast, high Treg levels have been reported in peripheral blood, lymph nodes, and tumour specimens from patients with different types of cancer. The present study discusses the polymorphisms located in intron, exon and promoter regions of FOXP3 which have already been investigated by many researchers. FOXP3 has received considerable attention in attempts to understand the molecular aspect of Treg cells. Therefore, in the present study, the relationship between genetic polymorphism of FOXP3 in Treg-cell role and in disease development are reviewed considering the interactive effect of genetic factors.
Journal of Genetics 04/2013; 92(1):163-71. · 1.09 Impact Factor
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ABSTRACT: Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFNγ signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFNγ in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFNγ and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFNγ (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFNγ mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFNγ axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.
Molecular Biology Reports 10/2012; · 2.93 Impact Factor
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ABSTRACT: The role of chemokines and the growth factors has been extensively analyzed both in cancer risk and tumor progression. The transforming growth factor beta (TGF-β) and chemokine (C-X-C motif) receptor 4 (CXCR4) genes are implicated in several diseases, including breast cancer. Genomic DNA was obtained from 21 samples of peripheral blood or from normal tissue, previously fixed in formalin and embedded in paraffin for TGF-β T869C polymorphism analyses. Total cellular RNA was extracted from the same 21 patients, but from fresh tissue (tumor and adjacent healthy from the same breast) for expression analysis by Real Time PCR. No significant differences were observed in genotype distribution according to clinicopathological characteristics. Transforming growth factor beta (TGF-β) mRNA expression was assessed according to T869C polymorphism and CC patients presented a higher TGF-β expression but not significant when compared to other genotypes (p = 0.064). A positive correlation was observed in relative mRNA expressions of CXCR4 and TGF-β (p = 0.020). It is known that overexpression of TGF-β by both tumor and stromal tissue can facilitate the development of metastases, mainly by TGF-β stimulated angiogenesis and increased tumor cell motility. Our findings suggested a role of these genes as progression markers for breast carcinoma.
Molecular Biology Reports 09/2012; · 2.93 Impact Factor
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ABSTRACT: J Oral Pathol Med (2012) 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.
Journal of Oral Pathology and Medicine 07/2012; · 1.63 Impact Factor
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ABSTRACT: Signals from the microenvironment have a profound influence on the maintenance or progression of breast cancer. In the present study, the frequency of CXCL12 rs1801157 polymorphism in peripheral blood and the expression of CXCL12, CXCR4 and IFNγ mRNA in normal and mammary gland tumor tissues were assessed in breast cancer patients. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism and expression analyses by quantitative RT-PCR. A lower CXCL12 mRNA relative expression was observed among allele A carriers when compared to GG carriers (p = 0.012). ER-positive breast cancer allele A carriers showed a significantly lower expression of CXCL12 mRNA within tumor tissue than in normal breast tissue when compared to GG ER-positive patients (p = 0.016). CXCR4 mRNA (p < 0.001) and CXCL12 mRNA (p = 0.02) relative expressions were significantly correlated with relative IFNγ mRNA expression. Allele A carriers presenting high levels of IFNγ had a significantly higher expression of CXCR4 mRNA in tumor tissue than GG patients (p = 0.026). It is possible that allele A carrier hormone receptor-positive patients could be more susceptible to metastasis development, since they present a lower CXCL12 expression in tumor tissue, and tumor cells expressing CXCR4 could migrate toward CXCL12 gradient. IFNγ expression increases in order to improve immune response and could favor higher CXCR4 expression leading to migration of cells, possibly of metastatic ones, too.
Clinical and Experimental Medicine 06/2012; · 1.58 Impact Factor
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João Paulo Souto Grando,
Hellen Kuasne, Roberta Losi-Guembarovski,
Iara Sant’Ana Rodrigues,
Henrique Mitsu Matsuda,
Paulo Emílio Fuganti,
Émerson Pereira Gregório,
Farid Libos Júnior,
Rodrigo Paes de Menezes,
Marco Aurélio de Freitas Rodrigues,
Ilce Mara de Syllos Cólus
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ABSTRACT: Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies
have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development
of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship
between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking
status. The GSTM1, GSTT1, CYP1A1 (A2455→G), and GSTP1 (A313→G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR
method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR)=1.35; 95% confidence interval (CI)=0.76–2.41 and OR=0.75; 95% CI=0.41–1.38, respectively].
Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR=1.77; 95% CI=1.01–3.12 and OR=1.99; 95% CI=1.07–3.73).
No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
Clinical and Experimental Medicine 04/2012; 9(1):21-28. · 1.58 Impact Factor
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Kalil William Alves de Lima, Roberta Losi Guembarovski,
Julie Massayo Maeda Oda,
Gyl Ramos,
Benedito Valdecir Oliveira,
Iglenir João Cavalli,
Enilze Maria de Souza Fonseca Ribeiro,
Marlene Silva Bardi Gonçalves,
Mateus Nobrega Aoki,
Sandra Odebrecht Vargas Nunes,
Maria Angelica Ehara Watanabe
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ABSTRACT: The serotonergic system may be involved in smoking behavior since the intake of nicotine increases serotonin secretion in the CNS. Moreover, evidence supporting the beneficial effect of selective serotonin reuptake for quitting smoking suggesting that the serotonin transporter (5-HTT) is a plausible target for the understanding and elucidation of smoking behavior. The transcriptional activity of its human gene (SLC6A4) is modulated by a polymorphism described in the second intron, the STin2 VNTR, which thus may interfere with 5-HTT synthesis. In this study was analyzed the polymorphism STin2 VNTR of 60 smokers male patients diagnosed for oral carcinoma, 61 male smokers without cancer and 65 non-smoker healthy blood donors. The STin2. 9 allele carriers were more present in smoker groups (with cancer and without cancer, respectively) than in the non-smoker (OR = 7.11, 95% CI = 0.83-60.91 and OR = 24.73; IC 95% = 3.17-192.66). Conversely, individuals carrying allele 10 were more prevalent in non-smokers compared with smokers (oral cancer patients and individuals without cancer, respectively), showing a protective factor of this allele (OR = 0.56; 95% CI = 0.24-1.33 and OR = 0.46; 95% CI = 0.20-1.07). This is the first report of a study assessing the importance of STin2 VNTR smoking behavior in Brazilian individuals and the association of STin2. 9 allele carriers in nicotine dependence. It is suggested that individuals with low serotonin concentration in the central nervous system, probably due to the presence of the allele for high expression of 5-HTT,especially STin2. 9, were more susceptible to nicotine dependence. Moreover, individuals with the 10 allele might have less risk for nicotine dependence.
Clinical and Experimental Medicine 05/2011; 12(1):13-9. · 1.58 Impact Factor
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ABSTRACT: The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.
Cytokine 05/2011; 55(2):260-5. · 3.02 Impact Factor
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ABSTRACT: The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06–2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21–2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability. In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer.
Cancer Investigation 11/2010; 28(9):917-24. · 1.85 Impact Factor
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Hellen Kuasne,,
Iara Sant’Ana Rodrigues,,
Paulo Emílio Fuganti,, Roberta Losi-Guembarovski,,
Kazuhiro Ito,,
Marina O. Kishima,,
Marco Aurélio de Freitas Rodrigues,,
Silvia Regina Rogatto,,
Rodrigo Mattos dos Santos,,
Ilce Mara de Syllos Cólus
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ABSTRACT: ABSTRACT The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androgen receptor (AR) genes were involved in prostate cancer risk and aggressiveness. Genotypes were determined by PCR-RFLP (PSA) or using a 377 ABI DNA Sequencer (AR). PSA(G/G) genotype (OR = 1.78, 95% CI = 1.06–2.99) and AR short CAG repeats (OR = 1.89, 95% CI = 1.21–2.96) increased risk for prostate cancer and were related with tumor aggressiveness. About 38.3% of tumors showed microsatellite instability. In conclusion, polymorphisms in these genes may be indicated as potential biomarkers for prostate cancer.
10/2010; 28(9):917-924.
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ABSTRACT: 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.
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.
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.
Some polymorphic variants analyzed can influence the development and the progression of prostate cancer.
Urologic Oncology 09/2010; 29(6):654-63. · 3.22 Impact Factor
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ABSTRACT: Data suggest that the serotonin (5-hydroxytryptamine, 5-HT) system is implicated in the pathogenesis of multiple neuropsychiatric disorders and may also be involved in smoking behaviour since nicotine increases brain serotonin secretion. It is known that smoking behaviour is influenced by both genetic and environmental factors. The present review examines the role of the serotonin transporter gene (5-HTT) in smoking behaviour and investigating studies that showed association of 5-HTT gene with smoking. This study discusses a polymorphism which has been investigated by many researchers, as the bi-allelic insertion/deletion polymorphism in the 5'- flanking promoter region (5-HTTLPR). This gene has received considerable attention in attempts to understand the molecular determinants of smoking. Therefore, in the present study, the relationship between genetic polymorphism of serotonin transporter in smoking behaviour is reviewed considering the interactive effect of genetic factors.
Journal of Genetics 04/2010; 90(1):179-85. · 1.09 Impact Factor
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Roberta Losi-Guembarovski,
Rodrigo Paes de Menezes,
Fernando Poliseli,
Vivian Nappi Chaves,
Hellen Kuasne,
Andrei Leichsenring,
Marcos Euzébio Maciel,
Alda Losi Guembarovski,
Benedito W Oliveira,
Gyl Ramos,
Lauro Toyshi Mizuno,
Iglenir João Cavalli,
Enilze Maria de Souza Fonseca Ribeiro,
Ilce Mara de Syllos Cólus
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ABSTRACT: Oral carcinoma is the sixth most frequent type of cancer in the world and the seventh most common in Brazil (the country with the highest incidence in Latin America). Mean five-year survival remains one of the lowest among the main cancers, thus justifying studies that contribute to the development of preventive strategies. The aim of this study was to compare the epidemiological, clinical, and histological characteristics of 91 patients with oral carcinoma. Mean age was 58.62 +/- 10.46 years, and male-to-female ratio was 6.6:1.0 (79 men and 12 women). European descendants predominated with 79 patients (86.8%). Eighty-five individuals (93.4%) smoked and 70 (76.9%) consumed alcohol regularly. Anatomical distribution of tumors was: 27 (29.7%) tongue; 18 (19.8%) floor of mouth; 11 (12.1%) oropharynx; and 11 (12.1%) oral mucosa. Fifty-seven patients (62.6%) presented lymph node involvement and three (3.3%) had distant metastases. Surgery and radiotherapy were used in 43.2% of patients. With the exception of the male/female ratio (which was higher), our data are consistent with previous studies on oral carcinoma patients.
Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública 03/2009; 25(2):393-400. · 0.83 Impact Factor
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João Paulo Souto Grando,
Hellen Kuasne, Roberta Losi-Guembarovski,
Iara Sant'ana Rodrigues,
Henrique Mitsu Matsuda,
Paulo Emílio Fuganti,
Emerson Pereira Gregório,
Farid Libos Júnior,
Rodrigo Paes de Menezes,
Marco Aurélio de Freitas Rodrigues,
Ilce Mara de Syllos Cólus
[show abstract]
[hide abstract]
ABSTRACT: Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case-control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455-->G), and GSTP1 (A313-->G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case-controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76-2.41 and OR = 0.75; 95% CI = 0.41-1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01-3.12 and OR = 1.99; 95% CI = 1.07-3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.
Clinical and Experimental Medicine 11/2008; 9(1):21-8. · 1.58 Impact Factor
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ABSTRACT: Genetic and epigenetic alterations in choroid plexus tumors, a rare neuroepithelial neoplasm most frequently detected in children, are poorly characterized. Epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Using methylation-specific polymerase chain reaction, the methylation patterns of the genes CDH1 (E-cadherin), RARB (retinoic acid receptor, beta), and SFN (stratifin; 14-3-3sigma) were retrospectively investigated in eight choroid plexus tumors (five papillomas, two atypical papillomas, and one carcinoma), as well as in two normal cortexes obtained after autopsy from male individuals aged 6 months and 64 years. Among the six pediatric tumors, the mean age at diagnosis was 1.8 years old (range, 0.2-6) and the two adult tumors were detected in a 66-year-old man and a 45-year-old woman. A high frequency of hypermethylation was detected in CDH1 and SFN genes in tumoral and normal cortex tissues. Tumor-specific RARB hypermethylation was observed in four papillomas. Further studies are required to evaluate the role of aberrant methylation in choroid plexus tumor progression.
Cancer Genetics and Cytogenetics 01/2008; 179(2):140-5. · 1.39 Impact Factor
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ABSTRACT: Interindividual differences concerning the risk of cancer development are mostly due to a genetically determined capacity of the organism, from bacteria to man, in activating and detoxifying carcinogens. Therefore, the association among specific alleles of enzymes that are able to metabolize chemical compounds and the risk of developing several cancers, is attributed to the existence of various enzymatic steps in biometabolism, which can result in the activation or detoxification of xenobiotics. A great part of detoxification genes which have already described, is related to Glutathione S- transferase (GSTs) enzyme family. GSTM-1 gene, which belongs to this family, is polimorfic in the population and occurs in about 30-50% of the individuals, depending on the ethnical group which they belong to. In several works described in literature, GSTM-1 gene has been frequently associated to a high risk of developing several types of cancer, mostly lung cancer. Such informations are extremely important in order to determine the frequency of this gene in different populations, searching for an identification of markers that indicate cancer susceptibility. Os seres humanos apresentam diferenças individuais quanto ao risco de desenvolver câncer. Tais diferenças são provenientes, entre outros fatores, da capacidade geneticamente determinada dos organismos, desde bactérias até o homem, em ativar e detoxificar os carcinógenos. Assim sendo, a associação entre alelos específicos de genes responsáveis pela metabolização de compostos químicos e o risco aumentado ao desenvolvimento de tumores, se deve à existência de múltiplos passos enzimáticos no metabolismo, que podem resultar na ativação ou detoxificação de xenobióticos. O maior grupo de genes de detoxificação já descritos até o momento envolve a grande família das enzimas Glutationa S-transferases (GSTs). O gene GSTM-1, que faz parte desta família, é polimórfico na população e ocorre em cerca de 30-50% dos indivíduos, dependendo do grupo étnico a que pertencem. Em diversos trabalhos descritos na literatura, o gene GSTM-1 vem sendo freqüentemente associado a um risco elevado de desenvolvimento de diversos tipos de tumores, principalmente o câncer de pulmão, o que torna de grande importância a determinação da freqüência deste gene nas diferentes populações, buscando a identificação de marcadores de susceptibilidade ao câncer.
Semina : Ciências Biológicas e da Saúde. 01/2001;
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Roberta Losi-Guembarovski,
Ilce Mara de Syllos Cólus,
Rodrigo Paes De Menezes,
Fernando Poliseli,
Vivian Nappi Chaves,
Hellen Kuasne,
Andrei Leichsenring,
Alda Losi Guembarovski,
Benedito W Oliveira,
Gyl Ramos,
Teresa C S Cavalcanti,
Lauro Toyshi Mizuno,
Iglenir João Cavalli,
Enilze Maria de Souza Fonseca Ribeiro
[show abstract]
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ABSTRACT: A case control association study was carried out to investigate polymorphisms in genes CYP1A1 (3801T > C), GSTM1, and GSTT1 (null genotypes) and oral squamous cell carcinoma (OSCC), including a correlation with some histopathological findings (tumor size, lymph node invasion and degree of tumor differentiation).
The patients (n = 91) and the controls (n = 81) were matched by age, sex, ethnicity and smoking habits. The molecular analysis was carried out using Polymerase Chain Reaction-Restrict Length Polymorphisms PCR-RFLP (CYP1A1) and Multiplex-PCR (GSTM1/GSTT1).
No association was found for any of the studied genes: CYP1A1 (odds ratio (OR) = 1.24; 95% Confidence Interval (CI) = 0.67-2.31), GSTM1 (OR = 0.61; CI 95% = 0.33-1.11), and GSTT1 (OR = 1.24; CI 95% = 0.65-2.38). The analysis of combining genotypes also showed lack of association. Comparison with the histopathological findings did not, in general, detect any statistically significant differences.
CYP1A1, GSTM1 and GSTT1 polymorphisms do not appear to influence the genetic susceptibility to OSCC or the progression to more advanced stages.
Anticancer research 28(2A):1023-8. · 1.73 Impact Factor
