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

Interactions among GSTM1, GSTT1 and GSTP1 polymorphisms, cruciferous vegetable intake and breast cancer risk.
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GSTM1、GSTT1 和 GSTP1 多态性、十字花科蔬菜摄入量和乳腺癌风险之间的相互作用。

DOI:
10.1093/carcin/bgm141
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发表时间:
2007
期刊:
影响因子:
4.7
通讯作者:
Gammon,MD
Gammon,MD
中科院分区:
医学2区
文献类型:
--
作者:
Steck,SE;Gaudet,MM;Britton,JA;Teitelbaum,SL;Terry,MB;Neugut,AI;Santella,RM;Gammon,MD

文献摘要

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异硫氰酸酯是十字花科蔬菜中发现的抗癌植物化学物质,它既能诱导谷胱甘肽S-转移酶(GST),又是GST的底物。GST是参与各种生物活性化合物代谢的II相代谢酶。GST基因的功能多态性已被确定,并可能与十字花科蔬菜的摄入量影响癌症的风险。我们使用长岛乳腺癌研究项目的数据检验了这一假设,长岛乳腺癌研究项目是1996年至1997年在纽约长岛进行的一项以人群为基础的病例对照研究。十字花科蔬菜的摄入量在过去一年中进行了评估,通过修改块食物频率问卷。采用多重聚合酶链反应(PCR)和Taqman方法检测1052例患者和1098例对照的GSTM 1、GSTT 1和GSTP 1 Ile 105 Val基因型。非条件logistic回归用于估计调整后的比值比(OR)和95%置信区间(CI)。我们发现GSTM 1 null、GSTT 1 null和GSTP 105 Ile/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),GSTM 1 present、GSTT 1 null和GSTP 1105 Ile/瓦尔+瓦尔/瓦尔基因型携带者OR降低36(OR = 0.64,95%CI = 0.42,0.97)。我们没有发现GST多态性和十字花科蔬菜摄入量与乳腺癌风险的联合作用。总之,我们发现了特定的三个GST基因多态性组合与乳腺癌风险之间的关联,但这些并没有改变十字花科蔬菜摄入量与乳腺癌之间的关联。需要更多的研究来证实观察到的相关性。
Isothiocyanates are anticarcinogenic phytochemicals found in cruciferous vegetables that both induce and are substrates for the gluthationeS-transferases (GSTs). The GSTs are phase II metabolizing enzymes involved in metabolism of various bioactive compounds. Functional polymorphisms inGSTgenes 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 andn= 1098 controls) and genotyped forGSTM1deletion,GSTT1deletion andGSTP1Ile105Val 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 theGSTM1null,GSTT1null andGSTP105Ile/Ile genotypes (OR = 1.86, 95% CI = 1.12, 3.08) and a 36% decrease in the OR among carriers ofGSTM1present,GSTT1null andGSTP1105Ile/Val + Val/Val genotypes (OR = 0.64, 95% CI = 0.42, 0.97) compared withGSTM1present,GSTT1present andGSTP1105Ile/Ile carriers. We found no joint effects amongGSTpolymorphisms and cruciferous vegetable intake and breast cancer risk. In conclusion, we found associations between specific combinations of threeGSTgene 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.