Krajinovic M, Ghadirian P, Richer C, Sinnett H, Gandini S, Perret C, Lacroix A, Labuda D, Sinnett D
Division of Hemato-Oncology, Charles-Bruneau Cancer Center, Sainte-Justine Hospital, University of Montreal, 3175 Côte Sainte Catherine, Montreal, Canada H3T 1C5.
Int J Cancer. 2001 Apr 15;92(2):220-5. doi: 10.1002/1097-0215(200102)9999:9999<::aid-ijc1184>3.0.co;2-h.
Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A14 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT110 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures.
乳腺癌是女性中最常见的恶性肿瘤。由于诸如BRCA1和BRCA2等遗传因素以及生育史仅构成30%的病因，环境暴露可能在乳腺癌的发生中起重要作用。同样，参与异生物（来自烟草烟雾、饮食或其他环境来源）生物转化的相关酶可能在乳腺癌致癌过程中发挥作用。由于代谢这些致癌物能力改变的个体患乳腺癌的风险可能不同，我们研究了细胞色素P - 450（CYP1A1、CYP2D6）、谷胱甘肽 - S - 转移酶（GSTM1、GSTT1、GSTP1）和N - 乙酰转移酶（NAT1、NAT2）基因变异在乳腺癌致癌过程中的作用。对149名患有乳腺癌的女性和207名健康对照者进行了一项病例对照研究，她们均为法裔加拿大人。发现CYP1A14等位基因是乳腺癌的一个重要风险决定因素（OR = 3.3，95% CI 1.1 - 9.7），特别是在绝经后女性中（OR = 4.0，95% CI 1.2 - 13.8）。吸烟者中NAT2快速乙酰化者的频率增加（OR = 2.6，95% CI 0.8 - 8.2），而NAT110等位基因使食用熟透肉类的女性患癌风险增加4倍（OR = 4.4，95% CI 1.0 - 18.9）。这些数据表明，CYP1A1*4、NAT1和NAT2变异通过改变外源性和/或内源性暴露的影响而参与乳腺癌的易感性。
