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[a]pyrene暴露和消化系统癌症的事件风险:从嵌套病例对照研究和不良结果途径网络分析的见解
1Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, China.
Journal of hazardous materials
|January 18, 2025
概括
甲 (B[a]P) 暴露与五种消化系统癌症的风险增加有关. 生物标志物显示B[a]P二醇环氧化 - 蛋白附加物与癌症的发展相关,可能通过细胞增殖和细胞亡途径的破坏.
科学领域:
- 环境健康 环境健康
- 癌症流行病学 癌症流行病学
- 分子毒理学 分子毒理学
背景情况:
- 甲 (B[a]P) 是已知的肺癌原体,但其在消化系统癌症 (DSCs) 和潜在机制中的作用尚未得到充分证实.
- 了解B[a]P暴露与DSC之间的联系对于公共卫生和癌症预防策略至关重要.
研究的目的:
- 为了研究B[a]P暴露之间的关系,用BPDE-Alb引物测量,和五个DSC的风险:食道,胃,结肠直肠,肝脏和胰腺癌.
- 探索潜在的常见致癌机制,包括参与B[a]P诱导癌症发展的分子途径.
主要方法:
- 在东-通吉队列中进行了五项嵌套病例控制研究.
- 选择了食道,胃,结肠直肠,肝脏和胰腺癌的病例,根据性别和年龄与健康对照进行了匹配.
- 测量了子[a]二醇环氧化蛋白 (BPDE-Alb) 添加物的血度,并分析了不良结果通路 (AOP) 网络.
主要成果:
- 在BPDE-Alb引物水平和所有五个DSC之间观察到显著的J形关联.
- 高BPDE-Alb暴露与食道癌 (2.19倍),胃癌 (2.14倍),结肠直肠癌 (1.67倍),肝癌 (2.40倍) 和胰腺癌 (1.78倍) 的发生风险增加有关.
- 对AOP网络的分析确定了涉及AhR和EGFR信号的关键事件,以及细胞增殖和细胞亡途径的失调.
结论:
- B[a]P暴露与五种主要消化系统癌症的风险增加有关.
- 细胞增殖和亡途径的破坏可能是B[a]P诱导的消化癌症发展的关键机制.
- 这些发现突显了B[a]P除了肺癌之外的致癌潜力,并表明DSCs的共同分子通路.
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