It was clear that with the exception of APC with the same high mutation rate from the initiation stage to the end stage of cancer, the KRAS, TP53, PIK3CA and SMAD4 gene mutation rates were elevated when malignancy developed (p < 0.05), and a significant increase of the positive rate on TP53 and PIK3CA from NNP, NP, early stage and late stage of carcinoma (7%, 15%, 33.3%, and 65% for TP53, p < 0.001; 0%, 0%, 23.3%, and 25% for PIK3CA, p = 0.002) were also observed. This evidence concerns the gene SMAD4 and cancer.