Overexpression of the c-myc proto-oncogene in colorectal carcinoma is associated with a reduced mortality that is abrogated by point mutation of the p53 tumor suppressor gene.
The survival of 119 colorectal cancer patients was analyzed in the light of the overexpression status of the c-myc proto-oncogene mRNA and the point mutation status of the p53 tumor suppressor gene in the primary adenocarcinoma. The presence of >3 fold overexpression of c-myc mRNA in the primary tumor was found to be associated with a better prognosis than patients who evinced no overexpression (P = 0.02, log rank analysis). Point mutation of the p53 tumor suppressor gene was found to be associated with a poorer patient prognosis (P = 0.007, log rank analysis). Endogenous levels of c-myc and point mutation of p53 both contributed independently toward a poorer patient prognosis in Cox regression modeling. The better prognosis seen in patients who overexpress c-myc was offset when c-myc overexpression was coupled with a point mutated p53 gene. These results suggest that in colorectal adenocarcinoma c-myc deregulation leads to increased apoptotic death, but that this response may be modulated by a more downstream event such as point mutation of the p53 gene.
Smith
D R
DR
Colorectal Cancer Research Laboratory, Department of Colorectal Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Republic of Singapore.
Goh
H S
HS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D015996:Survival Rate