RAS genes are commonly mutated in cancers yet despite many possible mutations, cancers have a ‘tropism’ towards a specific subset. As driver mutations, these patterns ostensibly originate from normal cells. High oncogenic RAS activity causes oncogenic stress and different oncogenic mutations can impart different levels of activity. Here we show that changing rare codons to common in the murine Kras gene to increase translation shifts tumors induced by the carcinogen urethane from arising from canonical Q61 to biochemically less active G12Kras driver mutations, despite the carcinogen still being biased towards generating Q61 mutations. Loss of p53 to blunt oncogenic stress partially reversed this effect, restoring Q61 mutations. Finally, transcriptional analysis revealed similar signaling amongst tumors driven by different mutations and Kras alleles. These finding suggest that the RAS mutation tropism of urethane is largely product of selection in normal cells for mutations promoting proliferation without causing oncogenic stress