Identifying Subsets of Complex Mixtures Most Associated With Complex Diseases Polychlorinated Biphenyls and Endometriosis as a Case Study
Identifying Subsets of Complex Mixtures Most Associated With Complex Diseases Polychlorinated Biphenyls and Endometriosis as a Case Study
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DOI：
10.1097/ede.0b013e3181ce946c
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发表时间：
2010-07-01
期刊：
影响因子：
5.4
通讯作者：
Carney, Ed
中科院分区：
文献类型：
--
作者：
Gennings, Chris;Sabo, Roy;Carney, Ed
背景资料：探索性的统计分析已进行流行病学数据集，其中的关系进行了检查暴露于多氯联苯（PCB）的混合物和妇女子宫内膜异位症的风险。在该研究中，子宫内膜异位症与4种抗雌激素多氯联苯（PCBs 105，114，126和169）的总和之间的关联是边缘显著的（P = 0.079），而与12种雌激素多氯联苯的总和之间没有发现关联（P = 0.681）。这一发现与普遍认为的子宫内膜异位症是一种雌激素依赖性疾病的观点不一致，促使进一步的统计分析，以探讨这些协会更details.Methods：作为一种替代方法的数据减少，一种优化算法被开发出来，以确定权重的线性组合的规模PCB水平，有最强的可能与子宫内膜异位症的风险。应用这种方法的抗雌激素PCB亚组显示，PCB 114负责近100%的协会。PCB 114在混合物中既不是最有效的也不是最丰富的抗雌激素的事实表明PCB 114可能是雌激素的，或者这种关联可能是由不同的机制驱动的。使用这种统计加权方法对12种雌激素多氯联苯进行进一步分析表明，与子宫内膜异位症的任何关联主要是由多氯联苯99和188以及其他一些可能的因素驱动的。虽然PCB混合物在子宫内膜异位症中的作用尚不清楚，这些结果表明，精细的统计方法与毒理学和生物学解释相结合，可以产生可检验的假设，否则就产生了。
Background: Exploratory statistical analyses have been conducted on an epidemiologic data set in which the relationship was examined between exposure to polychlorinated biphenyl (PCB) mixtures and risk of endometriosis in women. In that study, the association between endometriosis and the sum of 4 antiestrogenic PCBs (PCBs 105, 114, 126, and 169) was borderline significant (P = 0.079), whereas an association was not found (P = 0.681) with the sum of 12 estrogenic PCBs. This finding was inconsistent with the widely held notion that endometriosis is an estrogen-dependent disease, prompting further statistical analyses to explore these associations in more detail.Methods: As an alternative method of data reduction, an optimization algorithm was developed to determine weights in a linear combination of scaled PCB levels that has the strongest possible association with the risk of endometriosis.Results: Application of this method to the antiestrogenic PCB subgroup revealed that PCB 114 was responsible for nearly 100% of the association. The fact that PCB 114 is neither the most potent nor abundant antiestrogen in the mixture suggests that PCB 114 might be estrogenic or that the association may be driven by a different mechanism. Use of this statistical weighting method for further analyses of 12 estrogenic PCBs showed that any association with endometriosis was driven mainly by PCBs 99 and 188 and possibly a few others.Conclusion: Although the role of PCB mixtures in endometriosis remains unclear, these results demonstrate how the integration of refined statistical methods coupled with toxicologic and biologic interpretation can generate testable hypotheses that might not otherwise have been generated.