These results do not support the hypothesis that PFAAs are associated with clinically higher PSA. By inference, they may also fail to provide additional support for the hypothesis that PFAAs are associated with prostate cancer. Conversely, the absence of an association with PSA could be interpreted to argue against bias attributable to early detection and overdiagnosis,46 known to be associated with using the PSA test, as a potential contributing explanation for the PFAA studies that did find additional incident or matched prostate cancer cases.
Perfluorocarbon compounds including PFAAs have been found to have complex interactions with inflammatory systems in vivo and in vitro, and directly suppress some types of cytokine secretion by immune cells,47 while enhancing other types of immune response, such as mast cell release of histamine.48 The PSA test used for prostate cancer screening is considered to be affected by inflammation in the prostate gland,34 but whether that inflammation relates to predictive prostate cancer risk is less clear.49 This study does not support an effect of PFAAs on PSA, by inflammatory pathways or otherwise.
A strength of our approach is that we could achieve age- and other risk factor-adjusted associations of a variety of PFAAs in a large group of men, looking at a number of PFAA species in serum individually. The further ability to evaluate a “normal” value cutoff in the relevant age group moves the consideration from statistical association in a large population to whether the exposure is associated with clinical screening triggers. It is not associated. This study also has important weaknesses. It relies on one-time measures. These are likely to be representative of a long period in the case of the PFAAs with their very long half-lives, but may be less representative of PSA concentrations over time. Even for PFAAs, adult serum concentrations may not represent earlier and potentially critical periods of human development leading to increased risk of cancer. Prevalence data also inadequately represent the relationship of imperfect clinical biomarkers with incident cancer outcomes, even for cancers such as prostate cancer with generally long survival times. Nevertheless, incidence and case-control studies of PFAA exposure and prostate cancer already exist; this study was performed to inform those results regarding PSA findings only.
In summary, we sought but did not find a relationship of the most commonly encountered human serum PFAA concentrations with PSA.
The authors thank Linda Lilly (WVU School of Public Health) for manuscript support, and Jean Siebert (WVU Health Science Center Library and School of Public Health faculty) for advice about search strategies.
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