Article

Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer.

Molecular Oncology Unit, Portuguese Institute of Oncology-Oporto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal.
European Journal of Cancer (impact factor: 5.54). 06/2006; 42(7):958-63. DOI:10.1016/j.ejca.2006.01.015
Source: PubMed

ABSTRACT TP53 and its downstream effector gene P21 are two important genes in cell cycle regulation. Genetic alterations on p53 and attenuation of p21 expression result in progression through cell cycle G1 checkpoint, which can lead to cancer development. We analysed the frequency of TP53 codon 72 and 3'UTR P21 polymorphisms in 681 blood samples from 371 cervical cancer patients, 122 ovarian cancer patients and 188 healthy controls using AS-PCR and PCR-RFLP. Approximately twofold increased risk of ovarian cancer (OC) was observed for TP53 Pro carriers (P = 0.038), with a significantly higher risk for advanced OC (P = 0.018). Furthermore, among the P21 CC genotypes, TP53 P allele was also associated with a twofold increased risk of OC (P = 0.014) and to a threefold increased risk for advanced OC (P = 0.003) with an attributable proportion of 44.2%. These results were confirmed in an age-adjusted logistic regression analysis. No association was found between these polymorphisms and cervical cancer. Our results suggest that the TP53 codon 72 genotypes may be considered as a molecular marker, contributing to a genetic profile for ovarian cancer in women.

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Keywords

122 ovarian cancer patients
 
3'UTR P21 polymorphisms
 
371 cervical cancer patients
 
681 blood samples
 
age-adjusted logistic regression analysis
 
attributable proportion
 
cancer development
 
cell cycle G1 checkpoint
 
cell cycle regulation
 
cervical cancer
 
downstream effector gene P21
 
Genetic alterations
 
genetic profile
 
higher risk
 
ovarian cancer
 
P21 CC genotypes
 
p21 expression result
 
TP53 codon 72 genotypes
 
TP53 P allele
 
TP53 Pro carriers