血homocysteine水平和结直肠癌之间的因果关系:孟德尔的随机化研究
Xiaosong Ru1, Linjun Wu2, Yong Guo3
1Department of Traditional Chinese Medicine, Hebei General Hospital, Shijiazhuang, China.
Medicine
|November 15, 2025
概括
这项门德尔的随机化研究发现,同类氨酸 (Hcy) 水平与结直肠癌 (CRC) 风险之间没有因果关系. 虽然Hcy是潜在的干预目标,但需要进一步的研究来证实它在CRC开发中的作用.
科学领域:
- 遗传学和流行病学
- 癌症研究 癌症研究
- 代谢健康 代谢健康
背景情况:
- 高水平的同类氨酸 (Hcy) 与各种疾病有关,但其与结直肠癌 (CRC) 的因果关系尚不清楚.
- 了解这种关联对于开发针对性干预和CRC的预防策略至关重要.
- 之前的观察性研究已经表明了联系,需要强大的因果推理方法.
研究的目的:
- 为了研究基因预测的血homocysteine (Hcy) 水平和结直肠癌 (CRC) 的风险之间的潜在因果关系.
- 利用门德尔随机化 (MR) 作为一种强大的方法来推断因果关系,尽量减少混因素.
- 提供基于证据的洞察力,了解Hcy作为CRC的可修改风险因素.
主要方法:
- 使用孟德尔随机化 (MR) 分析,使用全基因组关联研究 (GWAS) 总结统计数据.
- 确定了与血Hcy水平作为仪器变量密切相关的单核酸多态 (SNPs).
- 利用逆变量 (IVW),MR-Egger和加权中位数方法,使用包括科克兰Q测试,MR-Egger截取和MR-PRESSO在内的灵敏度分析来评估异质性和性.
- 在两个独立的欧洲基于人口的数据集 (英国生物银行和FinnGen) 中验证了结果.
主要成果:
- 在英国生物库和芬恩基因数据集中的逆变异 (IVW) 分析显示,血Hcy水平和CRC风险之间没有统计学上显著的因果关系 (英国生物库:OR=0.9992,P=0.5951;芬恩基因:OR=0.9771,P=0.7698).
- MR-Egger和加权中位数分析也表明缺乏显著的因果关系.
- 灵敏度分析 (Cochran Q,MR-Egger拦截,MR-PRESSO) 证实没有显著的异质性和水平变性,支持研究结果的稳定性.
结论:
- 门德尔的随机分析没有证据表明血类固醇度和结直肠癌风险之间存在因果关系.
- 尽管Hcy是潜在的干预目标,但其在CRC发展中的直接因果作用似乎有限.
- 在更大,多样化的群体中进行进一步的验证是有必要的,以确定或驳斥这种关联.
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