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首页> 外文期刊>Frontiers in Oncology >Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case–Control Study within the Agricultural Health Study
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Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case–Control Study within the Agricultural Health Study

机译：性类固醇激素单核苷酸多态性，农药使用和前列腺癌的风险：农业健康研究中的嵌套病例对照研究

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Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation ( N ?=?1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies ( N ?=?17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p -values for interaction into q -values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 ( p -interaction?=?4.0?×?10~(?5); q -value?=?0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR?=?0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR?=?0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.
机译：实验和流行病学调查表明，某些农药可能会改变性类固醇激素的合成，代谢或调节，以及与激素相关的癌症的风险。在这里，我们评估了激素稳态中涉及的单核苷酸多态性（SNP）是否会改变农药暴露对前列腺癌风险的影响。我们评估了农业卫生研究队列中的776例病例和1,444例对照中39种农药与SNP之间与前列腺癌之间的农药-SNP相互作用。在这些相互作用中，我们包括了参与激素合成，代谢或调节的候选SNP（N = 1100），以及与循环性类固醇浓度相关的SNP（通过全基因组关联研究确定）（N = 17）。 。使用无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了乘性SNP-农药的相互作用。我们将用于交互的p值转换为q值，以反映多次比较，这反映了错误的发现率。我们观察到除草剂麦草畏和rs8192166之间在睾丸酮代谢基因SRD5A1之间存在显着的相互作用，这对多重比较测试是有鲁棒性的（p -interaction？=？4.0？×？10〜（？5）; q -value？=？ 0.03），因此具有两份野生型基因型CC的男性因使用低麦草畏（OR？=？0.62 95％CI：0.41，0.93）和大量使用麦草畏（OR而导致的前列腺癌风险降低）与未报告使用麦草畏的人群相比，α= 0.44，95％CI：0.29，0.68）;相反，在rs8192166上携带一或两个拷贝的变异T等位基因的人中，麦草畏与前列腺癌之间没有显着关联。此外，观察到两种有机磷酸酯杀虫剂和SNP之间与雌二醇代谢有关的相互作用导致前列腺癌的风险增加。尽管需要复制，但这些数据表明，由于接触农药和遗传易感性的结合，对循环激素的激动和拮抗作用都可能影响前列腺癌的风险。

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