Ahn Jiyoung, Gammon Marilie D, Santella Regina M, Gaudet Mia M, Britton Julie A, Teitelbaum Susan L, Terry Mary Beth, Neugut Alfred I, Eng Sybil M, Zhang Yuesheng, Garza Cutberto, Ambrosone Christine B
Department of Epidemiology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Carcinogenesis. 2006 Sep;27(9):1876-82. doi: 10.1093/carcin/bgl038. Epub 2006 Apr 19.
Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1A and GSTA1B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1B (variant) than that of GSTA1A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a population-based case-control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI)=1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend=0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI)=1.89 (1.09-3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers.
谷胱甘肽S-转移酶（GSTs）是II期酶，参与多种致癌物的解毒过程。新型GSTA1A和GSTA1B基因多态性导致表达差异，GSTA1B（变异型）的转录激活低于GSTA1A（常见型）等位基因。鉴于十字花科蔬菜可诱导GSTs，而GSTs可代谢烟草烟雾致癌物，我们推测变异型GSTA1B基因型可能使女性易患乳腺癌，尤其是在十字花科蔬菜摄入量低的女性和吸烟者中。因此，在基于人群的病例对照研究——长岛乳腺癌研究项目（1996 - 1997年）中，我们评估了GSTA1基因多态性与乳腺癌风险之间的潜在关系，同时考虑了蔬菜摄入量和吸烟状况。进行了基因分型（1036例病例和1089例对照），并评估了假定的乳腺癌风险因素和日常饮食摄入量。与具有常见的A/A基因型相比，具有GSTA1A/B或B/B基因型与乳腺癌风险增加无关。然而，在十字花科蔬菜摄入量处于最低两个三分位数的女性中，与具有A/*A基因型的女性相比，*B/B基因型与风险增加相关（每周0 - 1份时，OR（95%CI）=1.73（1.10 - 2.72））。在具有B/B基因型的女性中，观察到十字花科蔬菜摄入量与乳腺癌风险之间存在显著的负向趋势（趋势P值 = 0.05），较高的摄入量（每周4份以上）可减轻与该基因型相关的风险增加。与具有A/A基因型的从不吸烟者相比，具有B/*B基因型的当前吸烟者风险增加1.89倍（OR（95%CI）=1.89（1.09 - 3.25））。这些数据表明，与GSTA1表达降低相关的GSTA1基因型主要在十字花科蔬菜摄入量低的女性和当前吸烟者中与乳腺癌风险增加相关。
