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谷胱甘肽S-转移酶M1(GSTM1)、谷胱甘肽S-转移酶T1(GSTT1)和谷胱甘肽S-转移酶P1(GSTP1)基因多态性、十字花科蔬菜摄入量与乳腺癌风险之间的相互作用。

Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk.

作者信息

Steck S E, Gaudet M M, Britton J A, Teitelbaum S L, Terry M B, Neugut A I, Santella R M, Gammon M D

机构信息

Department of Nutrition, University of North Carolina, Chapel Hill, NC, 27599 USA.

出版信息

Carcinogenesis. 2007 Sep;28(9):1954-9. doi: 10.1093/carcin/bgm141. Epub 2007 Aug 11.

Abstract

Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthatione S-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms in GST genes have been identified and may interact with cruciferous vegetable intake to affect cancer risk. We examined this hypothesis using data from the Long Island Breast Cancer Study Project, a population-based case-control study conducted in Long Island, NY, from 1996 to 1997. Cruciferous vegetable intake in the previous year was assessed via modified Block food frequency questionnaire. DNA was extracted from blood samples (n = 1052 cases and n = 1098 controls) and genotyped for GSTM1 deletion, GSTT1 deletion and GSTP1 Ile105Val using multiplex polymerase chain reaction and Taqman assays. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI). We found an 86% increase in the OR for breast cancer among carriers of the GSTM1 null, GSTT1 null and GSTP 105Ile/Ile genotypes (OR = 1.86, 95% CI = 1.12, 3.08) and a 36% decrease in the OR among carriers of GSTM1 present, GSTT1 null and GSTP1 105Ile/Val + Val/Val genotypes (OR = 0.64, 95% CI = 0.42, 0.97) compared with GSTM1 present, GSTT1 present and GSTP1 105Ile/Ile carriers. We found no joint effects among GST polymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of three GST gene polymorphisms and breast cancer risk but these did not modify the association between cruciferous vegetable intake and breast cancer. Additional studies are needed to confirm the associations observed.

摘要

异硫氰酸盐是十字花科蔬菜中含有的抗癌植物化学物质,它既是谷胱甘肽S-转移酶(GSTs)的诱导剂,也是其底物。GSTs是参与多种生物活性化合物代谢的Ⅱ相代谢酶。已鉴定出GST基因中的功能多态性,其可能与十字花科蔬菜的摄入量相互作用,从而影响癌症风险。我们利用长岛乳腺癌研究项目的数据对这一假设进行了检验,该项目是1996年至1997年在纽约州长岛开展的一项基于人群的病例对照研究。通过改良的Block食物频率问卷评估前一年十字花科蔬菜的摄入量。从血样(1052例病例和1098例对照)中提取DNA,并使用多重聚合酶链反应和Taqman分析对GSTM1缺失、GSTT1缺失和GSTP1 Ile105Val进行基因分型。采用无条件逻辑回归来估计调整后的比值比(ORs)和95%置信区间(CI)。我们发现,GSTM1无效、GSTT1无效和GSTP 105Ile/Ile基因型携带者患乳腺癌的OR增加了86%(OR = 1.86,95% CI = 1.12,3.08),而与GSTM1存在、GSTT1存在和GSTP1 105Ile/Ile携带者相比,GSTM1存在、GSTT1无效和GSTP_1 105Ile/Val + Val/Val基因型携带者的OR降低了36%(OR = 0.64,95% CI = 0.42,0.97)。我们未发现GST多态性、十字花科蔬菜摄入量与乳腺癌风险之间存在联合效应。总之,我们发现三种GST基因多态性的特定组合与乳腺癌风险之间存在关联,但这些关联并未改变十字花科蔬菜摄入量与乳腺癌之间的关联。需要进一步的研究来证实所观察到的关联。

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