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  1. Article: Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility.

    Hatagima, Ana

    Cadernos de saude publica

    2002  Volume 18, Issue 2, Page(s) 357–377

    Abstract: Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered ... ...

    Abstract Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.
    MeSH term(s) Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP1A1/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; DNA Damage ; DNA Repair ; Endocrine System/drug effects ; Environmental Exposure/adverse effects ; Gene Expression Regulation/genetics ; Genes, Tumor Suppressor ; Genetic Predisposition to Disease ; Glutathione Transferase/genetics ; Glutathione Transferase/metabolism ; Humans ; Neoplasms/chemically induced ; Neoplasms/genetics ; Neoplasms/metabolism ; Polymorphism, Genetic ; Xenobiotics/adverse effects ; Xenobiotics/metabolism
    Chemical Substances Xenobiotics ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Glutathione Transferase (EC 2.5.1.18)
    Language English
    Publishing date 2002-08-16
    Publishing country Brazil
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1115730-6
    ISSN 1678-4464 ; 0102-311X
    ISSN (online) 1678-4464
    ISSN 0102-311X
    DOI 10.1590/s0102-311x2002000200002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4981: Show issues Location:
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  2. Article ; Online: Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility

    Hatagima Ana

    Cadernos de Saúde Pública, Vol 18, Iss 2, Pp 357-

    2002  Volume 377

    Abstract: Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered ... ...

    Abstract Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.
    Keywords Neoplasms ; Polymorphism (Genetics) ; Xenobiotic ; Endocrine Disruptors ; Medicine ; R ; Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2002-01-01T00:00:00Z
    Publisher Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility Polimorfismos genéticos e metabolismo dos desreguladores endócrinos na suscetibilidade ao câncer

    Ana Hatagima

    Cadernos de Saúde Pública, Vol 18, Iss 2, Pp 357-

    2002  Volume 377

    Abstract: Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered ... ...

    Abstract Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development. Estudos epidemiológicos estimam que cerca de 80% dos cânceres estão relacionados a fatores ambientais. A suscetibilidade individual ao câncer pode resultar de vários fatores relacionados ao metabolismo de xenobióticos, reparo do DNA, expressão de genes supressores de tumor e protoncogenes e estado nutricional. O metabolismo é o principal mecanismo para manter a homeostasia durante a exposição dos organismos aos xenobióticos. O equilíbrio das taxas de absorção e eliminação dos xenobióticos tem um papel importante na prevenção de danos no DNA, provocados por carcinógenos químicos. Sendo assim, a habilidade de metabolizar e eliminar os xenobióticos pode ser considerada uma das primeiras linhas de defesa dos organismos. Variações no metabolismo individual têm sido relacionadas aos polimorfismos enzimáticos, envolvidos na ativação e desintoxicação de carcinógenos químicos. Neste trabalho, é realizada uma revisão da literatura contemporânea sobre os polimorfismos genéticos envolvidos no metabolismo de ...
    Keywords Neoplasias ; Polimorfismos (Genética) ; Xenobióticos ; Desreguladores Endócrinos ; Neoplasms ; Polymorphism (Genetics) ; Xenobiotic ; Endocrine Disruptors ; Medicine ; R ; Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2002-04-01T00:00:00Z
    Publisher Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Renin-angiotensin system: is it possible to identify hypertension susceptibility genes?

    Lima, Sandro Gonçalves de / Hatagima, Ana / Silva, Norma Lucena Cavalcanti L da

    Arquivos brasileiros de cardiologia

    2008  Volume 89, Issue 6, Page(s) 427–433

    MeSH term(s) Disease Susceptibility ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hypertension/genetics ; Polymorphism, Single Nucleotide ; Renin-Angiotensin System/genetics ; Renin-Angiotensin System/physiology
    Language Portuguese
    Publishing date 2008-03-03
    Publishing country Brazil
    Document type Journal Article ; Review
    ZDB-ID 730261-7
    ISSN 1678-4170 ; 0066-782X
    ISSN (online) 1678-4170
    ISSN 0066-782X
    DOI 10.1590/s0066-782x2007001800013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Polimorfismos do gene NRAMP1 em indivíduos com reações hansênicas, atendidos em dois Centros de Referência no Recife, nordeste do Brasil.

    Teixeira, Márcia Almeida Galvão / Silva, Norma Lucena / Ramos, Alessandra de Luna / Hatagima, Ana / Magalhães, Vera

    Revista da Sociedade Brasileira de Medicina Tropical

    2010  Volume 43, Issue 3, Page(s) 281–286

    Abstract: Introduction: To investigate susceptibility to leprosy reactions, three polymorphisms of the natural resistance-associated macrophage protein (NRAMP1) gene were determined in 201 individuals who were attended at two reference centers in Recife, between ... ...

    Title translation NRAMP1 gene polymorphisms in individuals with leprosy reactions attended at two reference centers in Recife, northeastern Brazil.
    Abstract Introduction: To investigate susceptibility to leprosy reactions, three polymorphisms of the natural resistance-associated macrophage protein (NRAMP1) gene were determined in 201 individuals who were attended at two reference centers in Recife, between 2007 and 2008. Of these, 100 were paucibacillary and 101 were multibacillary.
    Methods: The 274C/T, D543N and 1729+55del4 polymorphisms of the NRAMP1 gene were determined using the technique of restriction fragment polymorphism on DNA extracted from peripheral blood. Allelic and genotypic frequencies were estimated by direct counting.
    Results: The predominant genotypes were: CC (51.8%) for 274C/T; GG (86.6%) for D543N; and +-TGTG (59.9%) for 1729+55del4. The mutant genotype 274 TT predominated in negativity of the reverse reaction (p = 0.03) and in positivity of erythema nodosum leprosum (p = 0.04).
    Conclusions: Our results suggest that 274 C/T polymorphism of the NRAMP1 gene may aid in determining the susceptibility to type II reactions among leprosy patients.
    MeSH term(s) Adolescent ; Adult ; Brazil ; Cation Transport Proteins/genetics ; Child ; Child, Preschool ; Female ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Infant ; Infant, Newborn ; Leprosy, Multibacillary/genetics ; Leprosy, Paucibacillary/genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic/genetics ; Polymorphism, Restriction Fragment Length ; Young Adult
    Chemical Substances Cation Transport Proteins ; natural resistance-associated macrophage protein 1
    Language Portuguese
    Publishing date 2010-05
    Publishing country Brazil
    Document type English Abstract ; Journal Article
    ZDB-ID 1038126-0
    ISSN 1678-9849 ; 0037-8682
    ISSN (online) 1678-9849
    ISSN 0037-8682
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  6. Article: Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in a Brazilian mixed population.

    Hatagima, Ana / Marques, Christiane F S / Krieger, Henrique / Feitosa, Mary F

    Human biology

    2005  Volume 76, Issue 6, Page(s) 937–942

    Abstract: The GSTM1 and GSTT1 null genotype frequencies were significantly different between 658 nonblack and black healthy blood donors from a Brazilian mixed population (Rio de Janeiro). The GSTM1 phenotype distribution was not in Hardy-Weinberg equilibrium in ... ...

    Abstract The GSTM1 and GSTT1 null genotype frequencies were significantly different between 658 nonblack and black healthy blood donors from a Brazilian mixed population (Rio de Janeiro). The GSTM1 phenotype distribution was not in Hardy-Weinberg equilibrium in either group, mainly because of an excess of the GSTM1*A/*B genotype.
    MeSH term(s) Adolescent ; Adult ; African Continental Ancestry Group/genetics ; Alleles ; Brazil ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency ; Genetic Variation ; Genetics, Population ; Genotype ; Glutathione Transferase/genetics ; Humans ; Male ; Middle Aged ; Phenotype ; Polymorphism, Genetic
    Chemical Substances glutathione S-transferase T1 (EC 2.5.1.-) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18)
    Language English
    Publishing date 2005-06-17
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1116-2
    ISSN 1534-6617 ; 0018-7143
    ISSN (online) 1534-6617
    ISSN 0018-7143
    DOI 10.1353/hub.2005.0018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population.

    Så, Renata Almeida de / Moreira, Aline Dos Santos / Cabello, Pedro Hernan / Ornellas, Antonio Augusto / Costa, Eduardo Butinhão / Matos, Cintia da Silva / Alves, Gilda / Hatagima, Ana

    International braz j urol : official journal of the Brazilian Society of Urology

    2014  Volume 40, Issue 4, Page(s) 463–473

    Abstract: Objective: To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the ... ...

    Abstract Objective: To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups.
    Materials and methods: We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP).
    Results: Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95% CI = 0.40-0.92) for PCa in comparison to genotype A / A.
    Conclusion: The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Brazil/ethnology ; Case-Control Studies ; Chi-Square Distribution ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Humans ; Isoenzymes/genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic/genetics ; Polymorphism, Restriction Fragment Length ; Prostatic Neoplasms/genetics ; Risk Factors
    Chemical Substances Isoenzymes ; glutathione S-transferase T1 (EC 2.5.1.-) ; GSTP1 protein, human (EC 2.5.1.18) ; Glutathione S-Transferase pi (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18) ; glutathione S-transferase alpha (EC 2.5.1.18)
    Language English
    Publishing date 2014-07
    Publishing country Brazil
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2206649-4
    ISSN 1677-6119 ; 1677-5538
    ISSN (online) 1677-6119
    ISSN 1677-5538
    DOI 10.1590/S1677-5538.IBJU.2014.04.04
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    Zs.A 6174: Show issues Location:
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  8. Article: Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: results from a case-control study in Rio de Janeiro.

    Marques, Christiane F S / Koifman, Sérgio / Koifman, Rosalina J / Boffetta, Paolo / Brennan, Paul / Hatagima, Ana

    Oral oncology

    2006  Volume 42, Issue 6, Page(s) 632–637

    Abstract: Xenobiotic metabolizing enzymes are involved in the detoxification of many carcinogens and may be important in modulating cancer susceptibility. CYP1A1, CYP2E1, GSTM3, and NAT2 polymorphisms were determined in peripheral blood DNA of 231 oral cancer ... ...

    Abstract Xenobiotic metabolizing enzymes are involved in the detoxification of many carcinogens and may be important in modulating cancer susceptibility. CYP1A1, CYP2E1, GSTM3, and NAT2 polymorphisms were determined in peripheral blood DNA of 231 oral cancer patients and 212 hospital controls in Rio de Janeiro, Brazil, using the PCR-RFLP technique. NAT2 polymorphism distribution was different between cases and controls (P=0.035), with an overrepresentation of NAT2( *)11 mutant allele in controls. Risk analysis showed that NAT2 4/4 individuals (OR=1.95, 95% CI=1.05-3.60) and combined GSTM3 and NAT2 heterozygotes (OR=1.94, 95% CI=1.04-3.66) were at increased oral cancer risk. No statistically significant association was observed for CYP1A1 and CYP2E1 polymorphisms. Our results suggest that NAT2 polymorphism, alone or combined with GSTM3, may modulate susceptibility to oral cancer in Rio de Janeiro.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aryl Hydrocarbon Hydroxylases/genetics ; Arylamine N-Acetyltransferase/genetics ; Brazil ; Case-Control Studies ; Cytochrome P-450 CYP1A1/genetics ; Cytochrome P-450 CYP2E1/genetics ; Female ; Genetic Predisposition to Disease ; Glutathione Transferase/genetics ; Humans ; Male ; Middle Aged ; Mouth Neoplasms/enzymology ; Mouth Neoplasms/genetics ; Polymorphism, Genetic ; Risk Assessment
    Chemical Substances Cytochrome P-450 CYP2E1 (EC 1.14.13.-) ; Aryl Hydrocarbon Hydroxylases (EC 1.14.14.1) ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; Arylamine N-Acetyltransferase (EC 2.3.1.5) ; NAT2 protein, human (EC 2.3.1.5) ; GSTM3 protein, human (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18)
    Language English
    Publishing date 2006-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 1368-8375 ; 0964-1955
    ISSN (online) 1879-0593
    ISSN 1368-8375 ; 0964-1955
    DOI 10.1016/j.oraloncology.2005.11.003
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    Zs.A 4869: Show issues Location:
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  9. Article ; Online: Superoxide dismutase, catalase, glutathione peroxidase and gluthatione S-transferases M1 and T1 gene polymorphisms in three Brazilian population groups.

    de Oliveira Hiragi, Cássia / Miranda-Vilela, Ana Luisa / Rocha, Dulce Maria Sucena / de Oliveira, Silviene Fabiana / Hatagima, Ana / de Nazaré Klautau-Guimarães, Maria

    Genetics and molecular biology

    2011  Volume 34, Issue 1, Page(s) 11–18

    Abstract: Antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX1) reduce the oxidation rates in the organism. Gluthatione S-transferases (GSTs) play a vital role in phase 2 of biotransformation of many substances. ... ...

    Abstract Antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX1) reduce the oxidation rates in the organism. Gluthatione S-transferases (GSTs) play a vital role in phase 2 of biotransformation of many substances. Variation in the expression of these enzymes suggests individual differences for the degree of antioxidant protection and geographical differences in the distribution of these variants. We described the distribution frequency of CAT (21A/T), SOD2 (Ala9Val), GPX1 (Pro198Leu), GSTM1 and GSTT1 polymorphisms in three Brazilian population groups: Kayabi Amerindians (n = 60), Kalunga Afro-descendants (n = 72), and an urban mixed population from Federal District (n = 162). Frequencies of the variants observed in Kalunga (18% to 58%) and Federal District (33% to 63%) were similar to those observed in Euro and Afro-descendants, while in Kayabi (3% to 68%), depending on the marker, frequencies were similar to the ones found in different ethnic groups. Except for SOD2 in all population groups studied here, and for GPX1 in Kalunga, the genotypic distributions were in accordance with Hardy-Weinberg Equilibrium. These data can clarify the contribution of different ethnicities in the formation of mixed populations, such as that of Brazil. Moreover, outcomes will be valuable resources for future functional studies and for genetic studies in specific populations. If these studies are designed to comprehensively explore the role of these genetic polymorphisms in the etiology of human diseases they may help to prevent inconsistent genotype-phenotype associations in pharmacogenetic studies.
    Language English
    Publishing date 2011-03-01
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 1445712-x
    ISSN 1678-4685 ; 1415-4757
    ISSN (online) 1678-4685
    ISSN 1415-4757
    DOI 10.1590/S1415-47572010005000102
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  10. Article: Glutathione S-transferase polymorphisms and oral cancer: a case-control study in Rio de Janeiro, Brazil.

    Hatagima, Ana / Costa, Emmerson C B / Marques, Christiane F S / Koifman, Rosalina J / Boffetta, Paolo / Koifman, Sergio

    Oral oncology

    2008  Volume 44, Issue 2, Page(s) 200–207

    Abstract: This study evaluates the influence of genetic polymorphisms at GSTM1, GSTT1 and GSTP1 gene loci on oral cancer susceptibility among Brazilians from Rio de Janeiro. DNA extracted from white blood cells of 231 oral cancer patients and 212 hospital controls ...

    Abstract This study evaluates the influence of genetic polymorphisms at GSTM1, GSTT1 and GSTP1 gene loci on oral cancer susceptibility among Brazilians from Rio de Janeiro. DNA extracted from white blood cells of 231 oral cancer patients and 212 hospital controls was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. GSTM1 polymorphism distribution was different between cases and controls (P=0.006), with an overrepresentation of GSTM1 A/B genotype in controls. GSTM1 A/B individuals were at decreased oral cancer risk (OR=0.08; 95% CI=0.05-0.62). No statistically significant association was observed for GSTT1 and GSTP1 polymorphisms. Differences in the GSTM1 and GSTT1 null genotype frequencies were observed between individuals of European origin and African origin, but these genotypes do not seem to influence the risk of oral cancer. Therefore, these results do not support the hypothesis of increased risk of GSTP1 G/G, GSTM1 or GSTT1 null genotypes for developing cancer in oral cavity, but the GSTM1 A/B genotype emerged as a protective factor.
    MeSH term(s) Adult ; Aged ; Brazil ; Carcinoma, Squamous Cell/enzymology ; Carcinoma, Squamous Cell/genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase/genetics ; Humans ; Isoenzymes/genetics ; Likelihood Functions ; Male ; Middle Aged ; Molecular Epidemiology ; Mouth Neoplasms/enzymology ; Mouth Neoplasms/genetics ; Polymorphism, Genetic
    Chemical Substances Isoenzymes ; glutathione S-transferase T1 (EC 2.5.1.-) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18)
    Language English
    Publishing date 2008-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 1368-8375 ; 0964-1955
    ISSN (online) 1879-0593
    ISSN 1368-8375 ; 0964-1955
    DOI 10.1016/j.oraloncology.2007.02.001
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