ABSTRACT

The carcinogenicity of perfluorooctanoic acid (PFOA) has been reviewed previously by several different regulatory agencies and researchers, with contradictory conclusions–especially regarding epidemiological findings on kidney cancer and testicular cancer. In addition, previous dose-response assessments have focused primarily on evidence from animal studies. This critical review summarizes peer reviewed epidemiological studies on PFOA and cancers of the kidneys and testes, using modified Hill’s criteria to assess the evidence for causation. We converted exposures to a common scale based on serum PFOA concentrations and applied meta-analysis to estimate the average increase in cancer risk reported by the studies with sufficient information to estimate serum PFOA. Using random effects meta-analysis, we found that the average relative increase in cancer risk per 10 ng/mL increase in serum PFOA for these studies is 16% (95% CI: 3%, 30%) for kidney cancer and 3% (95% CI: 2%, 4%) for testicular cancer. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies.

Implications: Our review meta-analysis indicates an average increase in cancer risk per 10 ng/mL increase in serum PFOA for kidney and testicular cancers. These associations are most likely causal, but results are limited by the small number of studies for testicular cancer, the overlapping study populations for several studies, and the lack of measured or modeled serum PFOA concentrations for several studies. The weight of evidence could be even stronger with the addition of future studies conducted in large cohorts.

摘要

全氟辛酸 (PFOA) 的致癌性先前已由几个不同的监管机构和研究人员进行过审查，得出的结论相互矛盾——尤其是关于肾癌和睾丸癌的流行病学发现。此外，以前的剂量反应评估主要集中在动物研究的证据上。这篇批判性评论总结了同行评审的关于全氟辛酸和肾癌和睾丸癌的流行病学研究，使用修改后的希尔标准来评估因果关系的证据。我们根据血清 PFOA 浓度将暴露量转换为通用量表，并应用荟萃分析来估计研究报告的癌症风险的平均增加，并提供足够的信息来估计血清 PFOA。使用随机效应荟萃分析，我们发现，在这些研究中，血清 PFOA 每增加 10 ng/mL，癌症风险的平均相对增加对于肾癌而言为 16%（95% CI：3%，30%）和 3%（95% CI：2%， 4%) 用于睾丸癌。这些关联很可能是因果关系，但结果受到睾丸癌研究数量少、几项研究的研究人群重叠以及几项研究缺乏测量或模拟的血清 PFOA 浓度的限制。

影响：我们的综述荟萃分析表明，肾癌和睾丸癌的血清 PFOA 每增加 10 ng/mL，癌症风险平均增加。这些关联很可能是因果关系，但结果受到睾丸癌研究数量少、几项研究的研究人群重叠以及几项研究缺乏测量或模拟的血清 PFOA 浓度的限制。随着未来在大型队列中进行的研究的加入，证据的权重可能会更大。