在结直肠癌中,生殖线倾向于瘤性基化损伤
Carino Gurjao1, Jules Cazaubiel2, Chichun Tan3
1Institute for Research in Immunology and Cancer Montreal Canada.
概括
患有MGMT rs16906252-T变异的个体由于化DNA损伤增加了结直肠癌 (CRC) 风险. 红肉消费协同增强了这种风险,建议有针对性的预防策略.
科学领域:
- 遗传学和癌症研究研究
- 分子流行病学分子流行病学
- 预防癌症 预防癌症
背景情况:
- 红肉消费是结肠直肠癌 (CRC) 的已知危险因素,与增加的化DNA损伤有关.
- rs16906252-T变体作为一个与沉默MGMT相关的cis表达定量特征位点 (eQTL),MGMT是修复化DNA损伤的关键基因.
- 这项研究假设rs16906252-T变种的携带者更容易受到化损伤引起的突变的影响.
研究的目的:
- 调查MGMT rs16906252-T变体与结直肠癌 (CRC) 中的化DNA损伤之间的关联.
- 为了检查红肉消费与rs16906252-T变异之间与CRC风险有关的相互作用.
- 探索化损害在CRC病变发生中的作用,特别是与特定突变和祖先有关的作用.
主要方法:
- 在来自大型CRC队列 (TCGA,NHS/HPFS,COCA-CN) 的全外因组测序数据上利用突变特征解卷.
- 分析了rs16906252-T变体和化依赖性瘤突变之间的关系.
- 综合生活方式数据,特别是红肉消费,以评估基因与环境的相互作用.
主要成果:
- 与非载体相比,rs16906252-T载体在CRC患者中显示出明显更高的瘤化损伤.
- 发现rs16906252-T变异在东亚祖先中很罕见,与这些人群中CRC患者的微不足道的化损伤相关.
- 化诱导的致癌性主要由KRAS G12D和G13D突变介导,在rs16906252-T和高摄入红肉之间观察到对瘤化损伤的协同效应.
结论:
- 携带MGMT rs16906252-T变异的携带者在CRC中易患瘤性化损伤,这种过程因食用红肉而加剧.
- 这些发现提供了证据,表明红肉和CRC之间存在因果关系.
- 这些结果可以指导开发个性化的饮食建议和查方案,以预防CRC.
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