We identified rare protein-truncating variants (PTVs) in the DNA damage response (DDR) genes BRCA2 (OR = 3.23 [2.65–3.90], P = 7.5 × 10−29) and ATM (OR = 2.92 [2.34–3.63], P = 1.17 × 10−19) and additionally rare damaging variants in SAMHD1 (OR = 2.02 [1.65–2.45], P = 2.36 × 10−11) as significantly associated with increased prostate cancer risk (Figs. 1, 2, Table 2, Supplementary Fig. 2 and Supplementary Data 3–4). Here, SAMHD1 is linked to prostate cancer.