RESUMO
Polymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4. The aim of this study was to use a population-based case-control study to investigate whether or not such genetic polymorphisms in EPHX1 gene can modify the relationship between smoking status and the risk of developing prostate cancer. We used restriction fragment length polymorphism, or PCR-RFLP to determine EPHX1 genotypes in subjects comprising 194 patients with histologically verified prostate cancer and 305 healthy individuals as control. We found no overall association between prostate cancer risk and functional polymorphisms of EPHX1 gene in exon 3 and exon 4. We further analysed the association between the EPHX1 genotypes and smoking. Smokers carrying the exon 3 Tyr/Tyr and Tyr/His genotypes were at no significant risk compared to non-smokers with the "rapid" Tyr/Tyr genotype. By contrast, a significant interaction of smoking and the exon 4 polymorphism was present.
Assuntos
Adenocarcinoma/genética , Epóxido Hidrolases/genética , Microssomos/enzimologia , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Fumar/genética , Adenocarcinoma/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Biotransformação/genética , Estudos de Casos e Controles , Éxons/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Risco , Eslováquia/epidemiologia , Fumar/epidemiologiaRESUMO
The aim of the paper is to determine whether IGF1, IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and one-nucleotide polymorphism in PSA and CYP17 gene might contribute to early diagnostics of prostate cancer (PCa). Serum level of PSA, IGF1 and IGFBP3 in the group of 158 individuals (92 PCa and 66 controls) was examined by RIA method and IGF1/IGFBP3 was calculated. PCR RLFP method was used to examine one- nucleotide polymorphism in PSA and CYP 17 gene. The results suggest that serum level of IGF1 over 95% CI did not increase relative risk of PCa development in overall group, not even regarding to particular investigated genotypes, not even if individuals with genotype AG+A1A1, AG+A1A2, GG+A1A1 and GG+A1A2 were evaluated. Serum level of IGFBP3 under 95% CI increased PCa relative risk in overall group(chi(2) = 10,03, p= 0,001, OR 3,12, 95% CI 1,44-6,93), as well as regarding to one-nucleotide polymorphism in individuals with PSA genotype AG(chi(2) = 4,72 p= 0,029, OR 2,87, 95% CI 01,09-7,49) and CYP 17 genotype A1A1(chi(2) = 3,76 p= 0,052, OR 2,57, 95% CI 0,97-6,75). The association between frequencies of occurrence of PCa and higher IGF1/IGFBP3 molar ratio was not confirmed, nor for gene polymorphism in PSA and CYP17, however OR (chi(2) = 1,58, p= 0,208, OR 1,67, 95% CI 0,75-3,71) was more than 1, nor in combination AG+A1A1,AG+ A1A2. Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and gene polymorphism in PSA and CYP17 gene might contribute to early diagnostics of PCa. Further research is needed to prove, whether serum level of IGFBP3 in addition to PSA determines the prognosis and progression of PCa.
Assuntos
Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Neoplasias da Próstata/sangue , Esteroide 17-alfa-Hidroxilase/genética , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Diagnóstico Precoce , Genótipo , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Masculino , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Radioimunoensaio , Risco , Fatores de RiscoRESUMO
Polymyositis is an inflammation of muscle tissue of unknown etiology. It is characterized by symmetric, mainly proximal muscle weakness, muscle fiber damage proved on biopsy, increased enzymes and myoglobin, and has corresponding electromyography findings. Other systems such as joints, lungs, heart, and gastrointestinal system are involved. Lung involvement is rather common. The most frequent symptom represents shortness of breath caused by muscle weakness. We report a case of a 66 year old woman with primary idiopathic polymyositis. The clinical state of the patient was complicated by progressive muscle weakness, dysphagia, and respiratory failure. Due to the ineffectiveness of the treatment with corticsteroids and cyclophosphamide, treatment with high doses of immunoglobulins was started. A total of 100 g of i.v. immunoglobulin therapy was administered beginning on the 13th day after hospital admission. The state of the patient progressively improved and after 7 weeks of treatment in a significantly improved state the patient was transferred to a Rehabilitation Unit. We therefore conclude that IVIg therapy may be an effective therapeutic approach for the treatment of acute complications of polymyositis, especially in cases in whom other therapeutic strategies are ineffective or harmful (Ref. 10). Full Text (Free, PDF) www.bmj.sk.