Kocabaş Neslihan Aygün, Sardaş Semra, Cholerton Suzanne, Daly Ann K, Karakaya Ali Esat
Department of Toxicology, University of Gazi, Pharmacy Faculty, Ankara, Turkey.
Int J Toxicol. 2004 Jan-Feb;23(1):25-31. doi: 10.1080/10915810490275053.
Increased exposure to environmental carcinogens, including several aromatic and heterocyclic amines (HAs), is suspected to be one factor contributing to incidence of breast cancer. The N-acetyltransferase 2 (NAT2) acetylation polymorphism have been associated with a number of drug-induced toxicities and cancer in various tissues, resulting from decreased capacity to activate/deactivate several aromatic amine, hydrazine drugs, as well as HA carcinogens. Ethnic differences exist in NAT2 genotype frequencies, which maybe a factor in cancer incidence. Our present case-control study in Turkey was performed to explore the association between NAT2 genetic polymorphism and individual susceptibility to breast cancer. The NAT2 genotypes (*4, *12A, *5A, *5B, *5C, *6, *7) were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 84 breast cancer patients and 103 healthy controls, and 50% and 56.3%, respectively, were found to be slow acetylator genotypes. There was no significant difference in risk for breast cancer development among patients with rapid and slow acetylators, with adjusted odds ratio 0.78 (95% confidence interval 0.44 to 1.38). Also, risk was not affected by different variables. To our knowledge, this is the first genetic study on the association of NAT2 genotypes with breast cancer in the TUrkish population, and this finding showed that NAT2 polymorphism does not play an important role in breast cancer risk of Turkish women by altering the capacity in deactivation of environmental carcinogens, even though small sample size and wide confidence interval.
接触包括几种芳香胺和杂环胺(HAs)在内的环境致癌物增加,被怀疑是导致乳腺癌发病率上升的一个因素。N - 乙酰基转移酶2(NAT2)乙酰化多态性与多种药物诱导的毒性以及不同组织中的癌症有关,这是由于激活/失活几种芳香胺、肼类药物以及HA致癌物的能力下降所致。NAT2基因型频率存在种族差异,这可能是癌症发病率的一个因素。我们目前在土耳其进行的病例对照研究旨在探讨NAT2基因多态性与个体对乳腺癌易感性之间的关联。使用聚合酶链反应 - 限制性片段长度多态性(PCR - RFLP)分析法在84例乳腺癌患者和103例健康对照中确定了NAT2基因型(*4、*12A、*5A、*5B、*5C、*6、*7),分别发现50%和56.3%为慢乙酰化基因型。快速和慢速乙酰化患者患乳腺癌的风险没有显著差异,调整后的优势比为0.78(95%置信区间为0.44至1.38)。此外,风险不受不同变量的影响。据我们所知,这是土耳其人群中关于NAT2基因型与乳腺癌关联的首次基因研究,这一发现表明,尽管样本量小且置信区间宽,但NAT2多态性通过改变环境致癌物失活能力,在土耳其女性乳腺癌风险中并不起重要作用。