Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200424
Type: Artigo de periódico
Title: Genes Of Detoxification Are Important Modulators Of Hereditary Medullary Thyroid Carcinoma Risk.
Author: Barbieri, R B
Bufalo, N E
Cunha, L L
Assumpção, L V M
Maciel, R M B
Cerutti, J M
Ward, L S
Abstract: Different inherited profiles of genes involved in cellular mechanisms of activation and detoxification of carcinogenic products can provide specific protection or determine the risk for cancer. Low-penetrance polymorphic genes related to the biotransformation of environmental toxins have been associated with susceptibility to and the phenotype of, human tumours. To investigate the role of germline inheritance of polymorphisms in CYP1A2*F, CYP1A1 m1, GSTP1, NAT2 and TP53 genes in hereditary medullary thyroid carcinoma (HMTC) patients. This study was developed in University of Campinas (Unicamp). We studied 132 patients with HMTC, 88 first-degree relatives of HMTC patients and 575 control individuals. All patients with MTC and their relatives were sequenced for the RET gene and five genes were genotyped using TaqMan(®) system. We observed that the inheritance of CYP1A2*F (OR = 2·10; 95% CI = 1·11-3·97; P = 0·022), GSTP1 (OR = 4·41; 95% CI = 2·47-7·88; P < 0·001) and NAT2 (OR = 2·54; 95% CI = 1·16-5·58; P = 0·020) variants increased the risk for HMTC. In addition, multiple regression analysis showed that the inheritance of GSTP1 polymorphisms was associated with the diagnosis in older patients (B = 8·0229; 95% IC = ± 5·5735; P = 0·0054). Concerning the group of HTMC relatives, CYP1A2*F (OR = 2:40; 95% CI = 1·19-4·86; P = 0·015), CYP1A1 m1 (OR = 2·79; 95% CI = 1:04-7·51; P = 0·042), GSTP1 (OR = 2·86; 95% IC = 1·53-5·32; P < 0·001) and NAT2 (OR = 2·25; 95% IC = 1·20-4·22; P = 0·012) were associated with HMTC risk. We have demonstrated that the inheritance of specific genes determining the individual response to environmental toxins may contribute to the risk and phenotypic variability that exists in patients with HMTC. Moreover, we identified a group at risk in relatives of HMTC patients.
Subject: Adolescent
Adult
Arylamine N-acetyltransferase
Cytochrome P-450 Cyp1a1
Cytochrome P-450 Cyp1a2
Female
Genetic Predisposition To Disease
Glutathione S-transferase Pi
Humans
Inactivation, Metabolic
Logistic Models
Male
Middle Aged
Phenotype
Polymorphism, Genetic
Proto-oncogene Proteins C-ret
Thyroid Neoplasms
Tumor Suppressor Protein P53
Rights: fechado
Identifier DOI: 10.1111/cen.12136
Address: http://www.ncbi.nlm.nih.gov/pubmed/23278115
Date Issue: 2013
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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