Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene

J Biochem Mol Toxicol. 2024 Nov;38(11):e70013. doi: 10.1002/jbt.70013.

Abstract

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

Keywords: cancer; detoxification; occupationally exposed; single nucleotide variant (SNV); stress biomarkers.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Female
  • Glucuronosyltransferase* / genetics
  • Glucuronosyltransferase* / metabolism
  • Humans
  • Lipid Peroxidation / drug effects
  • Middle Aged
  • Occupational Exposure / adverse effects
  • Oxidative Stress* / drug effects
  • Pesticides* / toxicity
  • Polymorphism, Single Nucleotide
  • Prognosis

Substances

  • Pesticides
  • Glucuronosyltransferase
  • UGT2B7 protein, human