The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of
breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and
protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in
breast cancer patients than in healthy controls: p',p' dichloro
diphenyl trichloroethane (
DDT), p'p' dichloro
diphenyl dichloroethane (
DDD),
endosulfan II,
delta-hexachlorocyclohexane (dHCH), and
heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of
cancer in Indian women. Proteomic analysis of plasma from
estrogen receptor-positive
breast cancer patients revealed 17 dysregulated
proteins, but
transthyretin (TTR) was three times higher than in healthy controls, which is further validated by
enzyme-linked
immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between
endosulfan II and the
thyroxine-binding site of TTR, pointing towards the significance of the competition between
thyroxin and
endosulfan, resulting in endocrine disruption leading to
breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.