【文献分享】The complexity of tobacco提供了数据和代码-CSDN博客

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吸烟，单独或与酒精混合，是头颈癌（HNC）的主要原因。我们通过对来自8个国家的265个全基因组测序的HNC样本进行突变特征分析，探讨了烟草暴露对癌症发展的影响。检测到六种与烟草相关的突变特征，包括一些以前未报道的。国家间HNC发病率的差异与烟草相关特征突变负担的差异相对应，这与烟草在HNC病因中的主导作用是一致的。在解剖亚位点之间发现了烟草相关特征负担的差异，表明组织特异性因素调节突变。我们确定了吸烟和酒精相关特征之间的联系，表明这些暴露的综合影响。吸烟与突变谱、癌症基因驱动突变库和拷贝数变化模式的差异有关。我们的研究结果表明，烟草烟雾可以通过多种途径影响癌细胞克隆的进化。

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). We explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC samples from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and alcohol-related signatures, indicating a combined effect of these exposures. Tobacco smoking was associated with differences in the mutational spectra, repertoire of driver mutations in cancer genes and patterns of copy number change. Our results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.