Fig. 6: CMV interacts with MM epidemiology in a BRAF-mutation-dependent manner.
a, CMV seropositivity of patients with cutaneous MM and stage II/III (age 40–70) versus those rates within UKB in white British aged 40–70 (adjuvant melanoma: n = 21; OR = 1.2; 95% CI, 0.44 to 3.02; P = 0.83; MM: n = 150; OR = 0.52; 95% CI, 0.36 to 0.74; P = 1.8 × 10−4; BRAF-WT: n = 82; OR = 0.58; 95% CI, 0.36 to 0.94; P = 0.026; BRAF mutant: n = 66; OR = 0.44; 95% CI, 0.25 to 0.76; P = 0.0018). All ORs and P values were obtained from a two-sided Fisher’s exact test. b, Presentation with cutaneous MM occurs significantly later in patients seropositive for CMV (left panel, 64 yr CMV− versus 71 yr CMV+, n = 252, P = 0.0014), while no significant difference is noted in other ICB-treated metastatic cancer (right panel, n = 53, P = 0.89). P values were derived from two-sided Wilcoxon rank sum tests; lower and upper box hinges represent the 25th to 75th percentiles, the central line represents the median and the whiskers extend to the highest and lowest values no greater than 1.5 × IQR. c, Relationship between age of presentation with MM and BRAF V600 mutation status according to CMV serostatus (left panel: BRAF V600 mutated, right panel: BRAF WT). There is no significant difference in age of presentation of BRAF-mutated patients according to CMV serostatus (n = 93, P = 0.33), whereas a highly significant effect is noted in patients with BRAF-WT MM (right panel, 65 yr CMV− versus 74 yr CMV+, n = 152, P = 1.3 × 10−4, two-sided Wilcoxon signed-rank test; boxplots as in c). d, Breakdown of BRAF mutation status versus CMV serostatus across all patients with cutaneous MM in the cohort (OR = 2.2; 95% CI, 1.2 to 3.9; P = 0.0054, two-sided Fisher’s exact test).
