Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA.
Pharmacogenet Genomics. 2011 Oct;21(10):615-23. doi: 10.1097/FPC.0b013e3283493a57.
To explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes.
[corrected] We evaluated pesticide-SNP interactions between 45 pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and 1444 controls in the Agricultural Health Study.
We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test.
A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase (GCLC; P interaction=1.0×10(-4)); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9-7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased prostate cancer risk was observed with high, compared with no, petroleum oil/petroleum distillate (OR=1.9, 95% CI: 1.1-3.2, P interaction=0.01; OR=2.1, 95% CI: 1.1-4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5-6.0, P interaction=2.0×10(-3)) use, respectively. No interactions were deemed noteworthy at the false discovery rate=0.20 level; the number of observed interactions in XMEs was comparable with the number expected by chance alone.
We observed several pesticide-SNP interactions in oxidative stress and phase I/II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.
为了探究前列腺癌与农业之间的关联，研究外源性物质代谢酶（XME）基因中农药使用与单核苷酸多态性（SNP）之间的关系十分重要。
在农业健康研究中，我们评估了 776 例病例和 1444 例对照中 45 种农药与 1913 种 XME SNPs 之间的农药-SNP 相互作用与前列腺癌的关系。
我们使用非条件逻辑回归来估计比值比（OR）和 95%置信区间（CI）。使用似然比检验计算 SNP-农药的相乘性相互作用。
与谷胱甘肽半胱氨酸连接酶（GCLC）中的 rs1883633 （P 交互作用=1.0×10(-4)）相比，石油油/石油馏分的使用与 rs1883633 之间呈正单调相互作用；携带至少一个变异等位基因（次要等位基因）的男性患前列腺癌的风险增加（OR=3.7，95%CI：1.9-7.3）。携带硫氧还蛋白还原酶 2（TXNRD2）rs4485648、微粒体环氧化物水解酶 1（EPHX1）rs17309872 或髓过氧化物酶（MPO）rs11079344 变体的男性中，与没有石油油/石油馏分相比，高剂量的石油油/石油馏分或特丁磷的使用与前列腺癌风险增加相关（OR=1.9，95%CI：1.1-3.2，P 交互作用=0.01；OR=2.1，95%CI：1.1-4.0，P 交互作用=0.01），或特丁磷（OR=3.0，95%CI：1.5-6.0，P 交互作用=2.0×10(-3)）。在错误发现率=0.20 水平上，没有认为有显著的交互作用；XME 中观察到的相互作用数量与仅由机会产生的相互作用数量相当。
我们观察到氧化应激和 I/II 相酶基因中存在一些农药-SNP 相互作用以及前列腺癌风险。需要进一步的研究来解释 XME 中的遗传变异、农药使用和前列腺癌风险的共同贡献。
