Role of the N-Acetyltransferase 2 Detoxification System in Thyroid Cancer Susceptibility
| Autor: | Alfio José Tincani, Ana Carolina Trindade Guilhen, Janaína Luisa Leite, Laura Sterian Ward, Natassia Elena Bufalo, Elaine Cristina Morari, Ligia V. M. Assumpção |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Arylamine N-Acetyltransferase Biology GSTP1 Risk Factors Internal medicine Genotype medicine Humans Genetic Predisposition to Disease Prospective Studies Thyroid Neoplasms Risk factor Thyroid cancer Genetics Haplotype Cancer Odds ratio Middle Aged medicine.disease Phenotype Haplotypes Polymyalgia Rheumatica Case-Control Studies Inactivation Metabolic Female Brazil |
| Zdroj: | Clinical Cancer Research. 15:406-412 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-08-1835 |
| Popis: | Purpose: Genetic polymorphisms in genes encoding for enzymes involved in the biotransformation of carcinogens have been shown to be relevant as risk for cancer and may be of considerable importance from a public health point of view. Considering that N-acetyltransferase 2 (NAT2) polymorphisms modulate the response to ionizing radiation, the strongest risk factor recognized to cause differentiated thyroid cancer (DTC) thus far, we sought to determine the influence of NAT2 detoxification system on thyroid cancer susceptibility. Experimental Design: We conducted a prospective case-control study, comparing 195 patients presenting with DTC that were previously genotyped for GSTT1, GSTM1, GSTP1, and CYP1A1, comprising 164 papillary carcinomas and 31 follicular carcinomas, with 196 control individuals paired for gender, age, ethnicity, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. We used PCR-RFLP assays and the combination of 6 variant alleles to define 18 NAT2 haplotypes that characterized slow, intermediate, or rapid phenotypes. Results: A multivariate logistic regression analysis identified the presence of *12A and the absence of *12B, *13, *14B, *14D, *6A, and *7A NAT2 haplotypes as risk factors for DTC. The inheritance of a rapid acetylation phenotype doubled the risk for a papillary carcinoma (odds ratio, 2.024; 95% confidence interval, 1.252-3.272). We found no relationship between genotypes and clinical, pathologic, or laboratory features of patients or between genotypes and outcome. Conclusions: We showed that NAT2 genotypes and the NAT2 rapid acetylation phenotype are important susceptibility factors for DTC, suggesting that NAT2 detoxification system is involved in this tumor pathogenesis. |
| Databáze: | OpenAIRE |
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