Figure 2: Burden analysis reveals distinct set of cancer susceptibility genes across 12 cancer types.

A total of 34 genes-of-interest were identified by burden analysis by comparing the frequencies of rare truncation variants in Caucasian cancer cases (n=3,125) versus their frequencies in the WHI control population (n=1,039). Two oncogenes (ABL2 and BCR) were omitted. (a) Significant genes across Pan-Cancer types. Data were analysed with the total frequency test (TFT) followed by false discovery rate (FDR) ranking. Dark horizontal line indicates the 5% FDR threshold, which is satisfied by five genes, including BRCA1, BRCA2, ATM, BRIP1 and PALB2. Inset shows closer visual resolution. (b) Significant genes for specific cancer types. Each plot shows the top tested genes, by FDR, from the same TFT analysis procedure for all 12 individual cancer types. Eight genes in addition to the five shown in a are significant at the 5% FDR level from cancer-type-specific analysis. (c) Cohort frequencies of genes. Bubble plot shows frequency of rare truncation mutation as a percentage of cases in each cohort (all 4,034 cases included for frequency calculation). The x-axis denotes the test group of a specific cancer type, the Pan-Cancer discovery cohort (4,034) and the validation cohort (1,627). Genes found to be significant at 5% FDR using the Pan-Cancer discovery cohort are labelled in boldface. Rings indicate genes that are significant (TFT, FDR ≤5%) for a particular cohort on the x-axis. (d) Percentage of cases carrying rare truncation in the 34 genes-of-interest across 12 cancer types in the discovery cohort.