PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.
PAH-DNA adducts, cigarette smoking, GST polymorphisms, and breast cancer risk.
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DOI：
10.1289/ehp.0800119
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发表时间：
2009-04
影响因子：
10.4
通讯作者：
Gammon MD
中科院分区：
文献类型：
--
作者：
McCarty KM;Santella RM;Steck SE;Cleveland RJ;Ahn J;Ambrosone CB;North K;Sagiv SK;Eng SM;Teitelbaum SL;Neugut AI;Gammon MD
多环芳烃（PAHs）可能会增加乳腺癌的风险，这种关联可能被谷胱甘肽s -转移酶（GSTs）在PAH中间体失活方面的遗传差异所改变。很少有乳腺癌研究调查了多种gst和多环芳烃生物标志物的联合作用。我们估计了GST基因（GSTA1、GSTM1、GSTP1和GSTT1）的多重多态性以及与多环芳烃dna加合物和吸烟的相互作用与乳腺癌风险相关。我们使用基于人群的女性样本（分别为病例/对照组）的数据进行了无条件逻辑回归：使用聚合酶链反应和基质辅助激光解吸/电离飞行时间试验对GST多态性进行了基因分型（n = 926 / 916），通过竞争性酶联免疫吸附试验测量了PAH-DNA加合物的血液水平（n = 873 / 941），通过现场问卷调查评估了吸烟状况（n = 943 / 973）。在至少有三个变异等位基因的女性中，可检测到多环芳烃- dna加合物的联合效应对乳腺癌风险的优势比为1.56[95%置信区间（CI）， 1.13-2.16]，未检测到加合物的联合效应的优势比为0.93 (95% CI, 0.56-1.56)；对于曾经吸烟的人，三个或更多变异的相应比值比为1.18 (95% CI, 0.82-1.69)，对于从未吸烟的人，相应比值比为1.44 （95% CI, 0.97-2.14）。两种交互作用均无统计学意义（p分别为0.43和0.62）。我们发现很少有统计学证据表明多环芳烃与GSTT1、GSTM1、GSTP1和GSTA1多态性相互作用，从而进一步增加乳腺癌风险。
Polycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker. We estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH–DNA adducts and cigarette smoking. We conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH–DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973). Odds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13–2.16] for detectable PAH–DNA adducts and 0.93 (95% CI, 0.56–1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82–1.69) for ever smokers and 1.44 (95% CI, 0.97–2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively). We found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk.
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影响因子：
8.3
作者：
Gammon, MD;Eng, SM;Santella, RM
通讯作者：
Santella, RM
影响因子：
6.4
作者：
Garter, Seymour;Taioli, Emanuela;Farmer, Peter
通讯作者：
Farmer, Peter
影响因子：
4.7
作者：
GRINBERGFUNES, RA;SINGH, VN;SANTELLA, RM
通讯作者：
SANTELLA, RM
影响因子：
6.1
作者：
Brescia, G;Celotti, L;Assennato, G
通讯作者：
Assennato, G
影响因子：
3.8
作者：
Hecht, Stephen S.;Carmella, Steven G.;Hatsukami, Dorothy K.
通讯作者：
Hatsukami, Dorothy K.