LBPO.BCS01 · 生物信息与计算 · Late-Breaking
结直肠癌中与西式饮食模式相关的突变特征
Mutational signatures associated with Western dietary patterns in colorectal cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
西式饮食模式是结直肠癌（CRC）的主要危险因素之一，但其对CRC基因组的突变影响仍不明确。我们整合了全基因组测序数据、饮食指标、患者调查和实验模型，以将西式饮食与特定突变过程联系起来。在来自11个国家的802例CRC中，肉类和脂肪消费的国家层面指标与两种特征的活性增加相关：反映5-甲基胞嘧啶脱氨基的SBS1，以及与活性氧相关的SBS18。SBS18的关联在一个外部CRC队列中得到独立验证，患者饮食调查证实较高的加工肉摄入与SBS1和SBS18活性升高相关。这两种特征占据了APC驱动突变的大部分，报告加工肉摄入较高的个体更可能携带APC驱动突变。在小鼠模型中，高脂喂养使肠上皮细胞中SBS1和SBS18的相对活性增加。总之，这些趋同的结果表明，西式饮食的摄入在CRC中留下了可检测的突变印记。
查看英文原文 English abstract
A Western dietary pattern is a major risk factors for colorectal cancer (CRC), yet its mutational impact on the CRC genome remains unclear. We integrated whole-genome sequencing data, dietary metrics, patient surveys, and experimental models to link Western diet to specific mutational processes. Across 802 CRCs from 11 countries, national measures of meat and fat consumption correlated with increased activity of two signatures: SBS1, reflecting 5-methylcytosine deamination, and SBS18, associated with reactive oxygen species. The SBS18 association was independently validated in an external CRC cohort, and patient dietary surveys confirmed that higher processed meat intake was linked to elevated SBS1 and SBS18 activities. These two signatures accounted for the majority of APC driver mutations, and individuals reporting higher processed meat intake were more likely to harbor APC drivers. In a mouse model, high-fat feeding increased SBS1 and SBS18 relative activity in intestinal epithelial cells. Together, these convergent results suggest that Western diet consumption leaves a detectable mutational footprint in CRC.
利益披露 Disclosure
M. Kazachkova, None..
T. Cattiaux, None..
A. Abbasi, None..
M. Meyenberg, None..
J. Loizou, None..
M. R. Stratton, None..
P. Brennan, None..
L. B. Alexandrov, None.