Linking TP53 codon 72 and P21 nt590 genotypes to the development of cervical and ovarian cancer.
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.
Molecular Oncology Unit, Portuguese Institute of Oncology-Oporto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal. alexandrambsantos@gmail.com
Alexandra M
AM
Santos
Hugo
H
Sousa
Daniela
D
Pinto
Catarina
C
Portela
Deolinda
D
Pereira
Raquel
R
Catarino
Isabel
I
Duarte
Carlos
C
Lopes
Rui
R
Medeiros
D016022:Case-Control Studies; D003062:Codon; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D003062:Codon; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53