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农药暴露和氧化应激的产生与 UGT2B7 基因中 rs7438135 等位基因变异的乳腺癌女性不良预后结果有关。

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.

机构信息

Laboratory and Clinical Physiopathology Program, State University of Londrina (UEL), Londrina, Paraná, Brazil.

Laboratory of Tumor Biology, State University of West Paraná (UNIOESTE), Francisco Beltrão, Paraná, Brazil.

出版信息

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.

摘要

农药暴露是多种疾病(包括乳腺癌)发展的风险因素。UGT2B7 酶参与农药解毒,基因中 rs7438135(G>A)变异增加其葡萄糖醛酸化潜力,有助于氧化应激代谢物的中和。在这里,我们根据 UGT2B7 rs7438135(G>A)状态,调查了 228 名乳腺癌女性的职业性农药暴露对全身氧化应激产生的影响。q-PCR 检测 rs7438135 变异的存在,并用等离子体测量氧化应激标志物(脂质过氧化水平、总抗氧化能力-TRAP 和一氧化氮代谢物-NOx)。在存在变异的情况下,农药暴露会导致多种临床病理条件下的全身脂质过氧化显著增加,包括增殖指数(ki67)高和侵袭性高的肿瘤。NOx 在高 ki67、孕激素受体阳性、高级别和三阴性/Luminal B 肿瘤以及低风险分层患者中增加。TRAP 在绝经前的年轻患者和三阴性/Luminal B 肿瘤患者以及死亡和复发风险低的分层患者中耗尽。这些发现表明,变异的存在并不能保护乳腺癌患者免受农药诱导的氧化应激产生的影响。

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