Costa Sandra, Medeiros Rui, Vasconcelos André, Pinto Daniela, Lopes Carlos
Unit of Molecular Oncology, Portuguese Institute of Oncology, Laboratórios - Piso 4, Rua Dr. Bernardino de Almeida, 4200-072 Porto, Portugal.
J Cancer Res Clin Oncol. 2002 Dec;128(12):678-82. doi: 10.1007/s00432-002-0391-9. Epub 2002 Nov 12.
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.
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.
The NAT26/NAT26 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 NAT26/NAT26 genotype was 10.2%.
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.
人乳头瘤病毒(HPV)是宫颈癌的主要致病因素。然而,其他风险因素也已被指出,包括致癌物暴露、口服避孕药的使用、某些营养缺乏以及遗传因素。N - 乙酰基转移酶2(NAT2)在几种致癌物的代谢中起重要作用。NAT2基因多态性通过O - 乙酰化激活或通过N - 乙酰化解毒来调节该酶的活性。本病例对照研究旨在评估NAT2基因多态性与宫颈癌遗传易感性之间的关联。
从125例晚期宫颈癌女性和170例健康女性中获取基因组DNA。采用聚合酶链反应 - 限制性片段长度多态性(PCR - RFLP)分析NAT2基因座的两个常见突变等位基因。
发现对应于慢乙酰化基因型的NAT26/NAT26基因型与宫颈癌风险增加3.41倍(95%可信区间:1.35 - 8.94;P = 0.007)相关。在整个病例组中,归因于NAT26/NAT26基因型的宫颈癌病例比例为10.2%。
本研究报告的结果表明,NAT2基因多态性是参与宫颈癌致癌过程的遗传易感性因素,并且对不同地理位置人群的等位基因谱分析可能有助于了解全球宫颈癌的发病率。