Role of the N-acetyltransferase 2 detoxification system in thyroid cancer susceptibility.
OBJECTIVE
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.


METHODS
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.
Guilhen
Ana C T
AC
Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences School, State University of Campinas, São Paulo, Brazil.
Bufalo
Natassia E
NE
Morari
Elaine C
EC
Leite
Janaina L
JL
Assumpcao
Ligia V M
LV
Tincani
Alfio J A
AJ
Ward
Laura S
LS
D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011111:Polymyalgia Rheumatica; D011446:Prospective Studies; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000235:genetics*
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human