Cumulative incidence, annual hazard rate of competing adverse events by age, and RP germline mutations in patients with cancer. (A) By age 30 years, no patients had developed AML, 3% had a ST, 20% had undergone a HSCT, and 13% had died. By age 45 years, 2% had developed AML, 12% had a ST, 24% had undergone a HSCT, and 23% had died of complications of stem cell transplantation (n = 25), iron overload (n = 18), infection/sepsis (n = 12), gastrointestinal cancer (n = 7), AML (n = 3), pulmonary embolism (n = 3), stroke (n = 2), or aplastic anemia (n = 2). The overall cumulative incidence of cancer (excluding MDS) was 13.7% by age 45 years. (B) Cause-specific hazard rates were as follows: HSCT or severe bone marrow failure occurred at a peak rate of just over 1% per year; deaths from complications of DBA began rising at age 20 years, peaking at almost 2% at 30 years of age; the rate of AML slowly increased beginning at age 40 years; and the rate of STs rapidly increased beginning at age 30 years. (C) DBA germline mutations in patients with cancer/MDS. Twenty of 39 patients with cancer/MDS had an RP gene mutation identified. The relative distribution of DBA in those with cancer genotyped was similar to that reported in the general DBA population with the most common genotypes represented. Due to the availability of only limited genetic testing in earlier patients who had died prior to mutation testing or could not undergo additional complete genetic testing, there were 49% with an unknown genotype. The general DBA population in the DBAR was genotyped (n = 214) as follows: RPS19 (45%), RPL5 (13%), RPS26 (11%), RPL11 (7%), RPL35A (7%), and RPS17 (5%). The significance, if any, of the absence of germline mutations in RPS26 in the cancer cohort is unknown at this time.