Potential increase in the prognostic value of p53 mutation by Pro72 allele in stage I non-small-cell lung cancer.
BACKGROUND
Accumulated evidence suggests that p53 function altered by its gene mutation or genetic polymorphism contributes to tumor malignancy. Association of p53 mutation and its codon 72 polymorphism with lung cancer prognosis has been extensively studied. However, the joint effect of p53 mutation and p53 codon 72 polymorphism on lung cancer prognosis remains uncertain.


METHODS
In the present study, 266 primary lung cancer patients were included and overall survival was calculated. Genomic DNA prepared from adjacent normal lung and lung tumor tissues was used to determine p53 codon 72 genotype and p53 mutation by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) and direct sequencing, respectively.


RESULTS
For all stages, neither p53 codon 72 genotype nor p53 mutation is associated with lung cancer prognosis. However, stage I patients with p53 mutation had a 1.79-fold hazard ratio [95% confidence interval (CI) 1.04-3.10] for overall survival when compared with p53 wild-type patients. Notably, stage I patients with p53 mutation and p53 codon 72 Pro/Pro genotype experienced a 2.66-fold hazard ratio (95% CI 1.21-5.85) for overall survival when compared with those with p53 wild-type and Arg/Arg genotype. An increased prognostic value was not observed in stage I patients with p53 wild-type and p53 Pro72 allele or in those with p53 mutation and p53 codon 72 Arg/Arg genotype.


CONCLUSIONS
We therefore suggest that p53 codon 72 Pro allele potentially increases the prognostic value of p53 mutation in stage I non-small-cell lung cancer.
Chien
Wen-Pin
WP
Lung Cancer Research Center, Chung Shan Medical University, Taichung, Taiwan, ROC.
Wong
Ruey-Hong
RH
Wu
Tsu-Chin
TC
Cheng
Ya-Wen
YW
Chen
Chih-Yi
CY
Lee
Huei
H
D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis