Implicações do polimorfismo genético de cyp1a1, gstm1 e gstt1 na suscetibilidade do carcinoma espinocelular da laringe
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2008-05-30
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Universidade Federal de Goiás
Resumo
The larynx is a tubular organ of the aerodigestive tract whose main function is the production of
voice, in addition to tasks related to the protection of the lower airways and swallowing food. The
squamous cell carcinoma presents itself as a multifactorial disease and epigenetic being influenced by
environmental factors, behavioural and relate to the individual. Several polymorphic genes that
encode enzymes involved in the biotransformation of the carcinogens have been associated to the
development of cancer, especially in squamous cell carcinoma of head and neck. The CYP1A1m,
GSTM1 and GSTT1 genes which catalyzes the oxidation of PAHs in phenolic and epoxides products.
The purpose of this study was to evaluate the epidemiological data of patients diagnosed with
squamous cell carcinoma of the larynx from the Cancer Registry of Population basis of Goiânia and
from Association of Cancer Combat in Goiânia, analyzing data from 63 medical records followed in a
period of 6 year; establish the allelic profiles of the gene CYP1A1m, GSTM1 and GSTT1 in casecontrol
groups investigating the degrees of suscetibility of patients diagnosed with squamous cell
carcinoma (SCC) of the larynx, according to smoking and alcoholism habits. In total 112 samples
were evaluated, 63 from patients with SCC of the larynx and 49 patients in the control group. The
CEC of the larynx was about 3,5 times more frequent in men than in women. The rate of survival on
general was approximately 66% to 6 years. The smoking and ethilic habits associated have a
significantly lower survival. No significant differences were found in the staging analysis and
treatment of patients. Were found allelic frequencies of CYP1A1m1 of 52,4% (34/62) and 63,3%
(31/49) for the wild allele T and 44,4% (28/62) and 34,7% (18/49) for the mutant allele C. There were
no statistically significant associations between allelic variants and genotypic CYP1A1m1 with
squamous cell carcinoma of the larynx. Positive genotypic frequencies were observed for the genes
GSTM1 and GSTT1 of 41.3% (26/63) and 54.0% (34/63) to the patients with laryngeal cancer, and
49,0% (24/49) and 51,0% (25/49) for the control group, respectively. For the assessment of genotype
GSTM1 (null) and GSTT1 (null), the patients if the case group had 58,7% (37/63) and 46,0% (29/63)
of genotypes for GSTM1 null and GSTT1, while the patients in the control group showed 51,0%
(25/49) and 40,8% (20/49). There was no statistically significance in associations of genotypic
variants GSTM1 (null) and GSTT1 (null) with the larynx squamous cell carcinoma. In this context, an
experimental study was accomplished in the intention of evaluating the function of the genes Cyp and
Gst in the metabolism of the Cyclophosphamide. This study addressed the Cyclophosphamide
toxicological evaluation and analysis of the polymorphism of Cyp2a29 and Gstp1 BALB/c genes in
mice, correlating them with the toxicity of drugs through the assessment of organs commonly affected.
It was determinated the DL50 of the 474mg/kg. Subsequently, another 40 mice were used on the
assessment of the genetic polymorphism of genes Cyp2a29 and Gstp1. As for toxicity,
cyclophosphamide caused reduction in body weight at different doses and kidneys, spleen, liver, heart
and lungs. The animals that received a dose of 500mg/Kg died in 24 hours, three animals with a dose
of 250mg/Kg died the end of one week. The evaluation of toxicity showed changes of varying degrees
of congestion observed in the spleen, liver and heart. There were not found statistically significant
differences between the frequencies of allelic and genotypic to Cyp2a29 and Gstp1 in groups of
animals studied. This observation should be probably the characteristic line BALB/c are isogenic.
Studies that make the use se of tests of genetic suscetibility, epidemic evaluation, combined to the
evaluation anatomopathological they allow the study of the interaction genetic atmosphere and a
possible standardization of various chemotherapy protocols for treatment.
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DA SILVA JUNIOR, R. L. Implicações do polimorfismo genético de cyp1a1, gstm1 e gstt1 na suscetibilidade do carcinoma espinocelular da laringe. 2008. 164 f. Dissertação (Mestrado em Biologia) - Universidade Federal de Goiás, Goiânia, 2008.