遗传和环境风险因素对不良肝脏结果的影响
Xinyuan Zhang1, Longgang Zhao2, Peter T Campbell3
1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
International journal of cancer
|December 4, 2025
概括
环境和遗传因素显著增加肝病和癌症风险,特别是当它们结合在一起时. 高环境风险对具有高遗传倾向的个体构成更大的威胁,强调需要个性化风险评估.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 遗传学 是一个遗传学.
- 环境健康 环境健康
背景情况:
- 在肝脏疾病和肝癌的发展中,遗传倾向和环境因素之间的相互作用尚未完全理解.
- 了解这些相互作用对于开发肝病的有效预防和治疗策略至关重要.
研究的目的:
- 研究不同遗传倾向的个体中环境因素与肝脏疾病和肝癌相关的程度.
- 分析遗传学环境 (G×E) 相互作用和人群归因风险 (PARs) 通过遗传风险分层的肝病.
主要方法:
- 利用了来自353703名参与者的英国生物库数据.
- 根据六个已知的风险因素计算了肝硬化多基因风险评分 (PRS) 和环境风险评分 (ERS).
- 分析了事件结果,包括与代谢相关的脂肪性肝病 (MASLD),肝硬化和肝癌,平均随访时间为13.6年.
主要成果:
- 无论是PRS还是ERS都对MASLD,肝硬化和肝癌的风险作出了重大贡献.
- 与PRS (13.3%) 相比,ERS对MASLD风险的贡献更高 (34.1%).
- 在肝硬化和肝癌中观察到显著的G×E相互作用,ERS在高PRS患者中构成更大的风险.
结论:
- 环境风险因素对肝病和癌症有明显的影响,特别是在具有高遗传倾向的个体中.
- 这些发现强调了风险分层和精准医学方法在治疗严重肝病方面的重要性.
- 在严重的肝病中,更强的G×E相互作用强调了综合基因和环境风险评估的必要性.
相关概念视频
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
169
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
169
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
203
Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
203
Cancer Prevention
7.6K
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
7.6K
Gene-Environment Interactions
1.0K
Gene expression is a dynamic process that is significantly influenced by environmental factors. This interaction underlies the complex nature of biological development and the phenotypic differences observed among individuals, even among those with identical genetic makeups. Factors such as radiation, temperature, behavior, nutrition, and stress play pivotal roles in determining how genes are expressed. The concept of the reaction range is central to understanding this interaction. It posits...
1.0K
Hepatic Drug Excretion: Influencing Factors
508
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
508
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug
196
In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
196


