Haplotype-tagging single nucleotide polymorphisms in the GSTP1 gene promoter and susceptibility to lung cancer.
Haplotype-tagging single nucleotide polymorphisms in the GSTP1 gene promoter and susceptibility to lung cancer.
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DOI：
10.1016/j.cdp.2009.02.004
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发表时间：
2009
影响因子：
--
通讯作者：
Spivack SD
中科院分区：
文献类型：
--
作者：
Tan XL;Moslehi R;Han W;Spivack SD
谷胱甘肽s -转移酶（GST） P1是人类肺部主要的II期异种代谢酶。我们的实验室之前在GSTP1基因启动子中发现了9个单核苷酸多态性（snp），然后根据统计推断将其分为三种主要的单倍型（Hap1， Hap2和Hap3）。Hap3表现出高表达表型。本研究的主要目的是通过克隆和测序实验确定GSTP1启动子单倍型与肺癌风险之间的关系。我们对150名肺癌患者和329名无个人病史的对照组进行了病例对照分析。统计推断的三个GSTP1启动子单倍型通过克隆和测序实验得到证实。选择单倍型标记snp，在调整混杂因素后，使用无条件逻辑回归测试GSTP1单倍型与肺癌的遗传相关性。利用似然比检验检验GSTP1启动子单倍型与吸烟或饮食中水果和蔬菜摄入量之间的统计互作。我们没有发现Hap3对肺癌的保护作用，尽管这一主要作用有充分的动力设计。标记Hap2的标签snp -1738 T >A和- 354g > T的纯合变体显示，与这些snp的纯合野生型相比，所有受试者以及水果和蔬菜摄入量低的个体患肺癌的风险增加（但统计学上不显著）。我们没有发现Hap2与水果和蔬菜的饮食摄入量之间有显著的相互作用。我们的研究结果不支持GSTP1启动子单倍型对该人群肺癌易感性的显著主效应和修饰效应，但强化了饮食摄入水果和蔬菜的保护作用。
Glutathione S-transferase (GST) P1 is a major phase II xenobiotic-metabolizing enzyme in the human lung. Our laboratory had previously identified nine single nucleotide polymorphisms (SNPs) in the GSTP1 gene promoter, which were then grouped into three main haplotypes (Hap1, Hap2, and Hap3) based on statistical inference. Hap3 was found to display a high expression phenotype. The main objective of the current study was to test the association between GSTP1 promoter haplotypes with the risk of lung cancer after determining the promoter haplotypes experimentally through cloning and sequencing. We conducted a case–control analysis of 150 subjects with lung cancer and 329 controls with no personal history of the disease. The three statistically inferred GSTP1 promoter haplotypes were confirmed experimentally through cloning and sequencing. Haplotype-tagging SNPs were selected and GSTP1 haplotypes were tested for genetic association to lung cancer using unconditional logistic regression after adjusting for confounders. Statistical interaction between GSTP1 promoter haplotypes with either cigarette smoking or dietary fruit and vegetable intake were tested using the likelihood ratio test. We did not find protective effects of Hap3 against lung cancer, despite an adequately powered design for this main effect. Homozygous variants of tagSNPs –1738 T >A and –354 G > T, which tag Hap2, showed an increased (but statistically non-significant) risk of lung cancer among all subjects as well as among individuals with low fruit and vegetable intake, compared to homozygous wildtypes for these SNPs. We did not find significant interactions between Hap2 and dietary intake of fruits and vegetables. Our results do not support significant main and modifying effects for GSTP1 promoter haplotypes on susceptibility to lung cancer in this population, but reinforce the protective effects of dietary intake of fruits and vegetables.
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影响因子：
168.9
作者：
London, SJ;Yuan, JM;Yu, MC
通讯作者：
Yu, MC
影响因子：
11.2
作者：
Cauchi, Stephane;Han, Weiguo;Spivack, Simon D.
通讯作者：
Spivack, Simon D.
影响因子：
2.1
作者：
Platz, EA;Krithivas, K;Giovannucci, E
通讯作者：
Giovannucci, E
DOI：
10.1097/00008571-199812000-00006
发表时间：
1998-12-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Jourenkova-Mironova, N;Wikman, H;Hirvonen, A
通讯作者：
Hirvonen, A
影响因子：
7.1
作者：
Lampe, JW
通讯作者：
Lampe, JW