Spitz M R, Duphorne C M, Detry M A, Pillow P C, Amos C I, Lei L, de Andrade M, Gu X, Hong W K, Wu X
Department of Epidemiology The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1017-20.
Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. One proposed mechanism for their protective action is through down-regulation of cytochrome P-450 biotransformation enzyme levels and induction of phase II detoxifying enzymes. Because ITCs also serve as a substrate for GSTs, we evaluated dietary intake of ITCs and GSTM1 and GSTT1 genotype information in a lung cancer case-control study. There were 503 newly diagnosed lung cancer cases (264 men and 239 women) identified from The University of Texas M. D. Anderson Cancer Center and 465 controls (252 men and 213 women) recruited from enrollees in a local managed care organization. Subjects had an in-person interview including a semiquantitative food frequency questionnaire, and blood samples were obtained for genotyping. Cases reported significantly lower ITC intake per day compared with controls (P = 0.009). There was no main effect associated with the GSTM1 null genotype [odds ratio (OR) = 1.09]. However, there was a statistically significant OR of 1.41 associated with the GSTT1 null genotype. On stratified analysis, low ITC intake and the GSTM1 null genotype were associated with increased lung cancer risk in current smokers, with an OR of 2.22 [confidence interval (CI) = 1.20-4.10). For current smokers with the GSTT1 null genotype, the OR with low ITC intake was 3.19 (CI = 1.54-6.62). The comparable OR in the presence of both null genotypes was 5.45 (CI = 1.72-17.22). These effects were not demonstrable for former smokers by GSTM1 genotype, although the risk for low ITC intake and GSTT1 null genotype was 1.79 (CI = 0.95-3.37). Thus, current smokers who are homozygous null for the GST null genotype and who consume less carcinogenic blocking compounds are at higher lung cancer risk. Some of the inconsistencies reported in the role of GST genotypes in lung cancer risk could be due to unexpected confounding from dietary factors.
异硫氰酸盐（ITCs）是十字花科蔬菜中的非营养性化合物，具有抗癌特性。其保护作用的一种推测机制是通过下调细胞色素P - 450生物转化酶水平并诱导II期解毒酶。由于ITCs也是谷胱甘肽S - 转移酶（GSTs）的底物，我们在一项肺癌病例对照研究中评估了ITCs的膳食摄入量以及谷胱甘肽S - 转移酶M1（GSTM1）和谷胱甘肽S - 转移酶T1（GSTT1）的基因型信息。从德克萨斯大学MD安德森癌症中心确定了503例新诊断的肺癌病例（264名男性和239名女性），并从当地一家管理式医疗组织的登记者中招募了465名对照者（252名男性和213名女性）。受试者接受了包括半定量食物频率问卷的面对面访谈，并采集血样进行基因分型。与对照者相比，病例报告的每日ITC摄入量显著更低（P = 0.009）。谷胱甘肽S - 转移酶M1无效基因型没有主要影响[比值比（OR）= 1.09]。然而，谷胱甘肽S - 转移酶T1无效基因型的OR值具有统计学意义，为1.41。分层分析显示，低ITC摄入量和谷胱甘肽S - 转移酶M1无效基因型与当前吸烟者患肺癌风险增加相关，OR值为2.22[置信区间（CI）= 1.20 - 4.10]。对于谷胱甘肽S - 转移酶T1无效基因型的当前吸烟者，低ITC摄入量的OR值为3.19（CI = 1.54 - 6.62）。两种无效基因型同时存在时的可比OR值为5.45（CI = 1.72 - 17.22）。对于既往吸烟者，根据谷胱甘肽S - 转移酶M1基因型未显示出这些影响，尽管低ITC摄入量和谷胱甘肽S - 转移酶T1无效基因型的风险为1.79（CI = 0.95 - 3.37）。因此，谷胱甘肽S - 转移酶无效基因型纯合且摄入较少致癌阻断化合物的当前吸烟者患肺癌的风险更高。在谷胱甘肽S - 转移酶基因型在肺癌风险中的作用方面报告的一些不一致情况可能是由于饮食因素意外的混杂作用。
