Influence of polymorphism at p53, CYP1A1 and GSTM1 loci on p53 mutation and association of p53 mutation with prognosis in lung cancer.
BACKGROUND
We previously found that the majority (9/11) of p53 tumor suppressor gene mutations in 60 lung cancer patients in Taiwan were small intragenic deletions and nonsense mutations. To gain insights into the possible etiologic factors involved in these mutations and the prognostic significance of p53 gene mutations in lung cancer in Taiwan, we investigated the influence of polymorphism at p53, cytochrome p450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) loci on p53 gene mutation, and the association of p53 gene mutation with prognosis in these lung cancer patients.


METHODS
The polymorphism of these genes was determined by polymerase chain reaction followed by restriction enzyme digestion. The Pearson chi 2 test was used to compare allelic distributions between lung cancer patients and controls. The log-rank test was used to assess the significance of the survival differences between patients with and without p53 mutations.


RESULTS
There was no significant difference with respect to the genotype distribution of p53, CYP1A1 and GSTM1 polymorphisms between patients with and without p53 mutations, although a tendency toward increasing frequency of the wild-type homozygote genotype of p53 polymorphism was noted in lung cancer patients containing p53 mutations. We further analyzed the association of p53 mutation with prognoses in lung cancer patients for whom postoperative survival data were available. The estimated median survival times for patients with and without p53 mutation were 25 and 28 months, respectively. There was no significant correlation between p53 mutation and survival.


CONCLUSIONS
Our data suggest that p53 gene mutation may not be associated with polymorphisms of p53, CYP1A1 and GSTM1 genes, and it may have no significant effect on the prognosis of lung cancer patients in Taiwan.
Institute of Toxicology, Chung Shan Medical and Dental College, Taichung, Taiwan, ROC.
Y C
YC
Wang
C Y
CY
Chen
H J
HJ
Wang
S K
SK
Chen
Y Y
YY
Chang
P
P
Lin
D002874:Chromosome Mapping; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D016158:Genes, p53; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D011110:Polymorphism, Genetic; D011379:Prognosis; D015996:Survival Rate
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase