TP73 alterations in cervical carcinoma.
Infection with human papillomaviruses (HPV) is essential in the carcinogenesis of the uterine cervix. However, a complex interrelation between viral and cellular genes is necessary for cell-cycle control deregulation and development and progression of cervical cancer induction. The TP73 gene is localized in 1p36.3 band, which is often deleted by loss of heterozygosity (LOH) in human cancers. We analyzed the p73 cytosine thymine polymorphism and LOH in this locus by polymerase chain reaction restriction fragment length polymorphism in 134 DNA samples from biopsies of 67 primary untreated invasive cervix tumors and the corresponding peripheral blood. Genotype frequencies of 56.7% for homozygous genotype GC/GC and 43.3% for heterozygous genotype GC/AT were found. The presence of the GC/AT genotype in tumors was associated with lower age at menarche (P=0.039) and high parity (P=0.015). In 20.0% of DNA tumor samples, the AT allele was lost compared with their DNA normal blood pairs. The AT allele was conserved in women with high parity. This was not the case in the group with low parity, with 33.3% of patients showing loss of the AT allele in tumor DNA (P=0.041). These results suggest that TP73 genetic alterations may contribute to the genesis and/or progression of cervical carcinoma in an HPV-infected transformation zone under prolonged exposure to events related to pregnancy.
Craveiro
Rogéria
R
Department of Radiotherapy, Instituto Português de Oncologia, Porto, Rua Dr. Ant. Bernardino Almeida, 4200-072 Porto, Portugal.
Costa
Sandra
S
Pinto
Daniela
D
Salgado
Lurdes
L
Carvalho
Luisa
L
Castro
Carla
C
Bravo
Isabel
I
Lopes
Carlos
C
Silva
Isabel
I
Medeiros
Rui
R
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D010298:Parity; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins