结直肠癌突变过程中的地理和年龄相关变异
Marcos Díaz-Gay1,2,3,4, Wellington Dos Santos5, Sarah Moody6
1Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
medRxiv : the preprint server for health sciences
|March 4, 2025
概括
结直肠癌的地理变异与不同的突变过程有关. 暴露于来自细菌的致变菌 colibactin 与早期结直肠癌发病率的增加有关.
科学领域:
- 基因组学就是基因组学.
- 癌症研究 癌症研究
- 微生物学 微生物学
背景情况:
- 结肠直肠癌 (CRC) 发病率显示出地理和时间的差异.
- 在全球范围内,早发性CRC (诊断年龄在50岁以下) 的显著增加已被观察到.
- 这些趋势的根本原因,特别是在早期发病的情况下,仍然在很大程度上是未知的.
研究的目的:
- 调查突变过程在地理和年龄相关CRC差异中的作用.
- 确定特定的变异原体及其对CRC发展的贡献,特别是在年轻人群中.
- 探索细菌变异原体和CRC中的驱动突变之间的联系.
主要方法:
- 来自11个国家的981个结直肠癌基因组的分析.
- 微卫星稳定 (MSS) 和微卫星不稳定 (MSI) 瘤中的突变负担和特征的比较.
- 特定突变特征的识别和量化,包括与 colibactin 相关的突变特征.
主要成果:
- 在不同国家的MSS结肠直肠癌病例中发现了突变负担和突变特征的显著差异.
- 归因于 colibactin 的突变特征 SBS88 和 ID18 在 CRC 发病率较高的国家更为普遍.
- 这些与大肠杆菌素相关的特征在早期发病的CRC中得到了丰富,并与APC驱动突变相关,这表明生命早期的暴露.
结论:
- 突变过程在结直肠癌中表现出地理和年龄相关的变化.
- 早期暴露于产生菌素的细菌可能是导致早期结直肠癌发病率上升的一个因素.
- 了解这些突变格局可以为有针对性的预防和治疗策略提供信息.
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