Occupational exposure to pesticides dysregulates systemic Th1/Th2/Th17 cytokines and correlates with poor clinical outcomes in breast cancer patients

Abstract

Pesticides are compounds known to cause immunetoxicity in exposed individuals, which have a potential to substantially modify the prognosis of pathologies dependent on an efficient immune response, such as breast cancer. In this context, we examined the circulating cytokine profile of Th1/Th2/Th17 patterns in women occupationally exposed to pesticides and their correlation with worse prognostic outcomes. Peripheral blood samples were collected from 187 rural working women with breast cancer, occupationally exposed or not to pesticides, to quantify the levels of cytokines IL-1β, IL-12, IL-4, IL-17-A, and TNF -α. Data on the disease profile and clinical outcomes were collected through medical follow-up. IL-12 was reduced in exposed women with tumors larger than 2 cm and in those with lymph node metastases. Significantly reduced levels of IL-17A were observed in exposed patients with Luminal B subtype tumors, with high ki67 proliferation rates, high histological grade, and positive for the progesterone receptor. Reduced IL-4 was also seen in exposed women with lymph node invasion. Our data show that occupational exposure to pesticides induces significant changes in the levels of cytokines necessary for tumor control and correlates with poor prognosis clinical outcomes in breast cancer.

Occupational pesticide exposure is linked to the prevalence of Luminal B breast cancer and poor prognosis features in Brazilian rural women

“…Due to its uncertain characteristics, intermediate risk may imply the recurrence of disease or even systemic damage and has been linked to poor immunological pro les. Other studies have reported immune deregulation in women exposed to pesticides, 38,39 which may favor the development of more aggressive tumors. For example, failure to produce Th1 immune responses can in uence the development of large tumor masses in the long term, potentially resulting in aggressive tumor behaviors, such as the occurrence of metastases observed in the exposed patients described in this study.…”

“…Further aggravating harm to the health of the population exposed to pesticides, a study conducted on a population chronically exposed to pesticides-even at low exposure doses-found an accumulation of DNA lesions due to failures in the genetic material repair system. 42 Thus, the accumulation of mutations observed in the immune and in ammatory responses triggered by pesticide exposure, 3,31,38,39 which generally result in the inactivation of tumor suppressor genes, are indications of genomic instability. 43 This genomic instability increases susceptibility to metastasis development.…”