MSH2 and neoplasm: When considering T stage and Gleason grade group as categorical rather than dichotomised variables, higher cumulative pLOF mutation carrier frequencies for the five genes associated with aggressive PrCa phenotypes (ATM, BRCA2, MLH1, MSH2, and NBN) were observed with both increasing tumour stage (P-trend = 3.9 × 10−12) and Gleason grade group (P-trend = 9.6 × 10−15), with the carrier frequencies in patients with T4 tumour stage or grade group 5 Gleason pattern being approximately three and a half times those with T1 or grade group 1 phenotypes (Supplementary Table 8 and Supplementary Fig. 2).