People with the highest levels of perfluorodecanoic acid (PFDA) in their blood have a 45% higher risk of developing cancers of the kidney, prostate, or bladder compared to those with the lowest...
Mechanism
Synthesis from 1 study
PFDA builds up in the kidneys, prostate, and bladder, where it blocks cell-to-cell communication, stops the body from flushing out harmful chemicals, and causes long-term inflammation. This mix of damage lets cells with broken DNA survive and multiply, eventually forming tumors.
Most probable mechanism
When PFDA builds up in the body, it gets into cells lining the kidney, prostate, and bladder, where it blocks the channels that let cells talk to each other, stops the body from removing harmful chemicals and hormones, and triggers long-lasting inflammation. This combination causes DNA damage, lets damaged cells survive instead of dying, and creates an environment where tumors can start growing.
PFDA enters epithelial cells of the kidney, prostate, and bladder through passive diffusion or membrane transporters.
PFDA binds to and disrupts connexin proteins that form gap junctions, impairing intercellular communication and calcium signaling.
PFDA inhibits UDP-glucuronosyltransferase enzymes, reducing the detoxification and elimination of carcinogens and estrogen metabolites.
Accumulation of unconjugated carcinogens and estrogen metabolites increases oxidative stress and DNA damage, including formation of 8-oxo-dG lesions.
PFDA activates the NLRP3 inflammasome, triggering sustained release of IL-1β and IL-18, which promotes chronic inflammation and tissue disorganization.
Oxidative stress and inflammatory signals suppress apoptosis and impair DNA repair mechanisms, allowing genetically damaged cells to survive and proliferate.
Persistent cellular damage, loss of tissue integrity, and uncontrolled growth create a microenvironment conducive to tumor initiation in genitourinary tissues.
Less supported by current evidence, but not ruled out
PFDA may alter chemical tags on DNA that control gene activity, turning off genes that normally prevent cancer and turning on genes that promote cell growth.
PFDA enters epithelial cells and interferes with enzymes that add methyl groups to DNA.
Global DNA hypomethylation and gene-specific hypermethylation occur, silencing tumor suppressor genes and activating oncogenes.
Epigenetic changes lead to increased cell proliferation, invasion, and genomic instability.
Evidence from Studies
Supporting (1)
Community contributions welcome
Perfluoroalkyl and polyfluoroalkyl substances and Cancer risk: results from a dose-response Meta-analysis
Contradicting (0)
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