Fig. 5: Alcohol-related signatures.

a, Mutational burdens of tobacco-related signatures in HNC cases sorted by subsite, alcohol and tobacco status. TMB per sample is also displayed. b, Mutational burdens for SBS, DBS and indel signatures showing positive associations with the tobacco plus alcohol status (n = 265 biologically independent samples). The Kruskal–Wallis test (two-sided) was used to test for global differences. Pairwise comparisons with the tobacco plus alcohol group were assessed with Dunn’s test (P values are shown in gray). Box-and-whisker plots are in the style of Tukey. The line within the box is plotted at the median, while the upper and lower ends indicate the 25th and 75th percentiles. Whiskers show 1.5× IQR. The y axes were cut at 1.25× upper whisker for clarity. Bar plots indicate the frequencies of dichotomized signatures. c, Associations between alcohol-related mutational signatures and the combined tobacco and alcohol exposures measured by logistic regression analysis. Regressions were corrected for sex, age of diagnosis, anatomical subsite and region. The Bonferroni method was used to adjust P values for multiple hypothesis testing. Effect size (log₂(OR), color) and significance level (−log₁₀(adjusted P), size). Dots filled in white indicate nonsignificant associations (Bonferroni-adjusted P < 0.05). OR, odds ratio.