European Journal of Obstetrics & Gynecology and Reproductive Biology
TP53 polymorphism at exon 4 in caucasian women from eastern France: lack of correlation with HPV status and grade of cervical precancerous lesions
Introduction
High risk human papillomaviruses (HPV) are recognized as the major etiological factors of cervical cancer [1], and an interaction of wild-type p53 with the E6 protein of HPV is thought to play a critical role in cervical carcinogenesis [2]. A common p53 polymorphism at codon 72 of exon 4 encoding either arginine (Arg) or proline (Pro) has been shown to affect E6-mediated degradation of p53 in vitro. The E6 protein forms stable complexes with p53 and promotes its degradation via the ubiquitin pathway [2]. Moreover, Storey et al. [3] have demonstrated a striking over-representation of TP53Arg homozygosity in cervical cancer patients compared with a healthy population in the United Kingdom. An association between p53 codon 72 polymorphism and the risk of squamous cell carcinoma of the cervix has also been proven in some Italian and Swedish population [4] as well as in Brazilian [5] and Greek populations [6], [7]. However, most independent studies conducted in larger groups with ethnic population homogeneity and various molecular techniques [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24] report contradictory results about the role of Arg variant as a risk factor for cervical cancer. Because squamous intraepithelial lesions (SIL) are believed to be premalignant lesions leading to invasive cancer [25], we decided to examine by the denaturant gradient gel electrophoresis (DGGE) technique the codon 72 TP53 polymorphism in women from eastern France with normal or abnormal cervical cytology.
Section snippets
Study population
Cervicovaginal specimens were collected in 1998–1999 for Pap smear and HPV testing from 138 women who attended the Department of Obstetrics and Gynaecology (University Hospital of Besançon, France). Only Caucasian French women were included in the study to avoid confounding factors due to ethnic differences. The mean age at presentation was 35 years (range: 16–76 years). After the Pap smear was obtained, cells from the transformation zone of the cervix and the endocervical canal were collected
HPV status and cytology characteristics
Of the 138 samples analyzed, 71 (51.45%) were found HPV positive. Low risk (LR) HPV were found in few samples (1.45%) while high risk (HR) HPV were detected in 65 cases, either alone (n=61) or in combination with LR HPV (n=4). Four samples harbored undetermined HPV (Table 1). In addition, the distribution of HR HPV type was related to cytology as reported in our previous data [26], and the prevalence of viral DNA increased with cytological abnormalities.
Genotypic distribution of TP53 gene
Fig. 1 shows the representative results
Discussion
HPV are recognized as the major etiological factors of cervical cancer [1]. The carcinogenic effect of HPV may be explained by the transforming viral protein E6 which binds to and induces the degradation of p53 through the ubiquitin pathway [2]. A common genomic polymorphism occurs at codon 72 of the TP53 gene, and results in translation of either arginine (Arg) or proline (Pro). In a recent report [3], Storey et al. demonstrated that the 72Arg form of the p53 protein appeared to be
Acknowledgements
This work was supported in part by grants from la Ligue contre le Cancer (Département du Doubs). We are grateful to Dr. Patrick Arveux and Nathalie Floret for helping with statistical analysis.
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