We uncovered significant differences in overall mutation rates, and in mutation rates in cytoskeletal protein‐related coding regions (CPCRs, including extracellular matrix protein coding regions), between nonsmokers and smokers in LUAD and HNSC (P < 0.001), raising the question of whether the CPCR mutation differences lead to different clinical courses for nonsmoker and smoker cancers. This evidence concerns the gene DNM2 and cancer.