Fig. 2: Geographic variation of mutational signatures in MSS colorectal cancers.

a, Variation of signature prevalence in specific countries compared to all others. Statistically significant enrichments were evaluated using multivariable logistic regression models adjusted by age of diagnosis, sex, tumour subsite and tumour purity. Firth’s bias-reduced logistic regressions were used for regression presenting complete or quasi-complete separation. Data points were coloured according to the odds ratio (OR), with size representing statistical significance. P values were adjusted for multiple comparisons using the Benjamini–Hochberg method based on the total number of signatures considered per variant type and the total number of countries assessed, and reported as q values. q values <0.05 were considered statistically significant and marked in red. b,c, Geographic distribution of the ID_J (b) and SBS_F (c) mutational signatures. Countries were coloured on the basis of signature prevalence. d, Association of signature activities with ASR. Statistically significant associations were evaluated using multivariable linear regression models adjusted by age of diagnosis, sex, tumour subsite and tumour purity. P values were adjusted for multiple comparisons using the Benjamini–Hochberg method based on the total number of signatures considered per variant type and reported as q values. Dashed lines indicate q values of 0.05 (orange) and 0.01 (red). e,f, Association of the mutations attributed to the SBS88 and ID18 mutational signatures with ASR across countries for colorectal cancer (e) and, independently, for colon and rectal cancers (f). Data points were coloured on the basis of signature prevalence, with size indicating the total number of cases per country. Statistically significant associations were evaluated using the sample-level multivariable linear regression models used in d (e) and similar models adjusted by age of diagnosis, sex and tumour purity (f). Blue lines and bands indicate univariate linear regressions and 95% confidence intervals for average signature activity versus ASR.