The Genetic Footprint of Tobacco Smoking: Unraveling the Mutational Signatures in Head and Neck Cancer

Abstract

Tobacco smoking and alcohol consumption are among the most significant, yet preventable, behavioral risk factors for cancer. In a recent paper in Nature Genetics, Torrens and colleagues performed whole-genome sequencing of 265 head and neck cancer (HNC) samples collected from eight countries across Europe and South America. They investigated the mechanisms underlying HNC development using mutational signature analysis and driver mutation analysis, complemented by regression analysis with epidemiological data. While the analyses confirmed the established roles of tobacco smoking and alcohol consumption as the primary causes of HNC, key findings included the synergistic effect of tobacco smoke and alcohol consumption, and that alcohol-induced mutational burden was significantly higher when combined with tobacco smoking. Additionally, the difference in smoking habits between countries was identified as a direct contributor to regional differences in HNC incidence. Furthermore, a novel smoking-related mutational signature SBS_I was discovered, awaiting further investigation into the underlying mutational process. This genomics-driven work by Torrens and colleagues evokes further research interest regarding the precise mechanisms of tumor initiation and promotion, and in the field of public health measures. In the end, Torrens and colleagues conclude with a call for anti-smoking measures, emphasizing the need to combat this major cancer risk factor.