A slow acetylator genotype associated with an increased risk of advanced cervical cancer.
OBJECTIVE
Human papillomavirus (HPV) is the major etiological agent associated with cervical cancer. However, other risk factors have been indicated, including carcinogen exposure, oral contraceptive usage, certain nutritional deficiencies, and genetic factors. N-acetyltransferase 2 (NAT2) has an important role in the metabolism of several carcinogens. NAT2 polymorphism modulates the activity of the enzyme, by activation, via O-acetylation, or through detoxification, via N-acetylation. This case-control study was designed to evaluate the association between NAT2 polymorphism and genetic susceptibility to cervical cancer.


METHODS
Genomic DNA was obtained from 125 women with advanced cervical cancer and 170 healthy women. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms) was used to analyse two common mutant alleles at NAT2 loci.


RESULTS
The NAT2*6/NAT2*6 genotype, which corresponds to a slow acetylator genotype, was found to be associated with a 3.41-fold (95% CI: 1.35-8.94; P= 0.007) increase in the risk of cervical cancer. For the entire case groups the proportion of cervical cancer cases attributable (attributable proportion) to the NAT2*6/NAT2*6 genotype was 10.2%.


CONCLUSIONS
The results reported in this study suggest that NAT2 polymorphism is a genetic susceptibility factor involved in the carcinogenesis of cervical cancer, and also that the analysis of the allelic profile of populations in different geographic locations may help to understand the incidence of cervical cancer worldwide.
Costa
Sandra
S
Unit of Molecular Oncology, Portuguese Institute of Oncology, Laboratórios - Piso 4, Rua Dr. Bernardino de Almeida, 4200-072 Porto, Portugal. sandracostas@hotmail.com
Medeiros
Rui
R
Vasconcelos
André
A
Pinto
Daniela
D
Lopes
Carlos
C
D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
D004273:DNA, Neoplasm; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human