In an analysis of the subset of 14,050 individuals with cancer for whom it was possible to determine that DNA was likely obtained before or at the time of diagnosis and prior to treatment with radiation or chemotherapy for a primary tumor (designated as “likely untreated”), we observed a stronger association between mosaic abnormalities and non-hematological cancer diagnosis (OR=1.45, 1.18-1.80 95% CI, p=0.0005). The associations for lung and kidney also increased in significance (Table 3). It is notable that the evidence for association with non-hematological cancer diminished in individuals who were potentially treated (OR=1.03, 0.81-1.30 95% CI, p=0.80). We had approached this analysis with the hypothesis that there could be an increased frequency in detectable clonal mosaicism in non-hematological cancers induced by chemotherapy or radiotherapy but were surprised to observe the frequency was reduced to virtually the same as in the cancer-free population. Although this attenuated effect could have many explanations (e.g., related to the diagnosis and treatment of a solid tumor leading to a decrease in populations of cells with mosaic alteration), we had a limited capacity to model
