Mitochondrial DNA copy number mediated the associations between perfluoroalkyl substances and breast cancer incidence: A prospective case-cohort study
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View abstract on PubMed
Summary
This summary is machine-generated.This study found that exposure to perfluorononanoic acid (PFNA) and perfluoroheptanoic acid (PFHpA) increased mitochondrial DNA copy number (mtDNAcn), which in turn elevated breast cancer risk. mtDNAcn mediated the link between PFHpA exposure and breast cancer.
Area Of Science
- Environmental Health
- Molecular Epidemiology
- Toxicology
Background
- Per- and polyfluoroalkyl substances (PFASs) are linked to breast cancer, but mechanisms remain unclear.
- Mitochondrial DNA copy number (mtDNAcn) is implicated in carcinogenesis.
- Investigating mtDNAcn as a mediator can clarify PFASs-breast cancer associations.
Purpose Of The Study
- To examine the association between plasma PFASs and blood mtDNAcn.
- To assess the relationship between mtDNAcn and breast cancer risk.
- To quantify the mediating role of mtDNAcn in PFASs-breast cancer pathways.
Main Methods
- A case-cohort study (226 cases, 990 sub-cohort) within the Dongfeng-Tongji cohort.
- Measured plasma concentrations of six PFASs and blood mtDNAcn using LC-MS/MS and qPCR.
- Employed linear regression, weighted Cox models, and mediation analysis.
Main Results
- Elevated blood mtDNAcn observed with higher PFNA and PFHpA exposure.
- High mtDNAcn levels significantly increased breast cancer risk (HR=3.34).
- mtDNAcn mediated 14.6% of the PFHpA-breast cancer association.
Conclusions
- PFNA and PFHpA exposure are associated with increased mtDNAcn.
- mtDNAcn plays a mediating role in the PFHpA-breast cancer relationship.
- Findings offer insights into biological mechanisms linking PFASs and breast cancer.
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