ABSTRACT
A pancreatite crônica é uma desordem complexa, na qual a interação entre fatores ambientais e genéticos resulta na enfermidade. O presente estudo incluiu 148 pacientes com diagnóstico de pancreatite crônica, 110 etilistas crônicos e 297 controles sadios com o objetivo de investigar a frequência de tabagismo e das mutações N34S e P55S do gene SPINK1 e R254W do gene CTRC nesta população. Foi aplicado questionário presencial e realizada reação de sequenciamento para a pesquisa das mutações genéticas, após assinatura do Termo de Consentimento Livre e Esclarecido. Os portadores de pancreatite crônica possuíam etiologia alcoólica em 74% das vezes e idiopática em 26%. A pancreatite alcoólica apresentou-se de maneira distinta da pancreatite crônica idiopática, sendo que o primeiro grupo é composto por maior prevalência do gênero masculino (88,18% versus 34,21%), por maior média de idade (55,64 anos versus 45,20 anos), menor frequência de caucasianos (63,89% versus 84,21%), menor escolaridade (23,30% concluíram ensino médio ou superior versus 57,89%) e maior frequência de repercussões da doença, como diarréia (54,21% versus 24,24%), emagrecimento (56,07% versus 24,24%), diabete melito (57,94% versus 36,36%) e ocorrência de pseudocistos pancreáticos (31,78% versus 12,12%), repercussões estas que não foram acompanhadas de maior frequência de alterações morfológicas, como calcificações pancreáticas ou dilatação do ducto pancreático principal. A frequência de tabagismo foi significativamente maior em pacientes com pancreatite crônica alcoólica do que em etilistas sem pancreatite crônica, podendo ser considerado cofator de risco para o desenvolvimento da pancreatite crônica entre alcoolistas (p = 0,002); a frequência da mutação N34S do gene SPINK1 em pacientes com pancreatite crônica foi de 3,38%, maior do que a frequência de 0,49% encontrada nos grupos controle (p = 0,016); a frequência de 2,03% da mutação P55S do gene SPINK1 e a frequência de 0,67% da mutação...
Chronic pancreatitis is a complex disorder in which the interaction between environmental and genetic factors results in the disease. This study included 148 patients with chronic pancreatitis, 110 chronic alcoholics and 297 healthy controls in order to investigate the frequency of smoking and N34S and P55S mutation of SPINK1 gene and R254W of CTRC gene in this population. A questionnaire was applied and gene sequencing was done, after having the Informed Consent Statement. Those with chronic pancreatitis had alcoholic etiology in 74% of cases and idiopathic in 26%. Alcoholic pancreatitis presented in a distinct way of idiopathic chronic pancreatitis. The first group is composed of a higher prevalence of males (88.18% versus 34.21%), by higher mean age (55.64 years versus 45.20 years), lower frequency of Caucasians (63.89% versus 84.21%), lower education (23.30% completed secondary or higher education versus 57.89%) and worst impact from the disease such as diarrhea (54.21% versus 24.24%), weight loss (56.07% versus 24.24%), diabetes mellitus (57.94% versus 36.36%) and occurrence of pancreatic pseudocysts (31.78% versus 12 , 12%). These effects were not accompanied by increased frequency of morphological changes, such as pancreatic calcifications or dilation of the main pancreatic duct. The frequency of smoking was significantly higher in patients with alcoholic pancreatitis than in alcoholics without chronic pancreatitis, therefore tabagism may be considered as a cofactor for the development of chronic pancreatitis among alcoholics (p = 0.002); the frequency of N34S mutation of SPINK1 gene in patients with chronic pancreatitis was 3.38%, higher than the rate of 0.49% found in the control groups (p = 0.016); the frequency of 2.03% of the P55S mutation of SPINK1 gene and the frequency of 0.67% of the CTRC gene R254W mutation found in patients with chronic pancreatitis were not statistically different when compared to the frequencies of 0.49%...
Subject(s)
Humans , Male , Female , Alcoholism , Genetics , Pancreatitis, Chronic , Smoking , Trypsin Inhibitor, Kazal PancreaticABSTRACT
<p><b>OBJECTIVE</b>To study the expression and prognostic significance of ERG and SPINK1 expression in endocrine-treated prostatic cancer.</p><p><b>METHODS</b>Prostatic needle biopsies from 118 prostatic cancer patients primarily treated with endocrine therapy were reviewed. Immunohistochemical study for ERG and SPINK1 protein was carried out.</p><p><b>RESULTS</b>Co-expression of ERG and SPINK1 was not observed. The frequency of ERG protein expression in the 118 biopsies studied was 9.3% (11/118). The positive expression correlated with T stage (P=0.04) but not with patient age at diagnosis, prostatic specific antigen level, Gleason's score, M stage, tumor area and progression-free survival. Positive expression of SPINK1 was demonstrated in 11.0% (13/118) of the biopsies. SPINK1-positive cases carried a significantly shorter progression-free survival, as compared with SPINK1-negative cases (P=0.022). The expression was not associated with any other clinicopathologic variables. The following expression pattern showed statistically significant correlation with the clinical progress (P=0.029): ERG+/SPINK1- (11/118, 9.3%), ERG-/SPINK1+ (13/118, 11.0%) and ERG-/SPINK1- (94/118, 79.7%).</p><p><b>CONCLUSIONS</b>ERG and SPINK1 proteins are mutually exclusive.SPINK1 expression is associated with more aggressive clinical behavior and can serve as a prognostic biomarker in prostatic cancer.</p>
Subject(s)
Aged , Aged, 80 and over , Humans , Male , Middle Aged , Antineoplastic Agents, Hormonal , Therapeutic Uses , Carrier Proteins , Metabolism , Disease-Free Survival , Follow-Up Studies , Immunohistochemistry , Neoplasm Grading , Neoplasm Staging , Prognosis , Prostatic Neoplasms , Drug Therapy , Metabolism , Pathology , Trans-Activators , Metabolism , Transcriptional Regulator ERG , Trypsin Inhibitor, Kazal PancreaticABSTRACT
Chronic pancreatitis is not one disease; it is a pathway of injury and fibrosis driven by many factors. The role of genetics is emerging as a major factor, both in terms of understand pathogenesis, and in terms of identifying risk factors and mechanisms. Use of the TIGAR-O classification system, or others will be useful research tools to determine gene-gene, gene-environment, and other interactions that contribute to development of an otherwise mysterious disease