Early Reportp53 codon 72 polymorphism and risk of cervical cancer in UK
Introduction
A candidate marker for risk of cervical cancer risk was described earlier this year.1 Such a marker could be used to direct high-risk women to more frequent cervical screening. The investigators found that a polymorphism at codon 72 of the p53 gene, resulting in the substitution of arginine for proline in the gene product, increased the susceptibility of p53 protein to degradation by E6 protein derived from oncogenic human papillomaviruses (HPV). These findings suggest that the two p53 isoforms are functionally different. This theory was examined in a pilot study, which found that the frequency of the arginineencoding allele was significantly higher in normal tissue from 30 women with cervical cancer than in 41 healthy controls; 76% of cervical cancer cases were homozygous for the arginine polymorphism compared with 37% of controls.
To confirm the results of this study, we examined the p53 codon 72 polymorphism genotypes of a larger series of women. Apart from the previously described study,1 there are no reports of the frequency of the arginine allele in any UK population. Because the frequency of the arginine allele varies between ethnic groups,2 the validity of such a study depends on accurate matching of cases and controls.
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Participants and samples
Ethics committee approval was obtained for this study. To keep any selection bias to a minimum, the distribution of p53 codon 72 genotypes was examined in two different UK white control populations: 96 women from different parts of the UK who had volunteered to take part in a randomised controlled trial of ovarian-cancer screening and 150 women attending for routine antenatal care in the Oxford region of the UK who were also taking part in a study of the genetics of asthma. 50 white women who
Results
The frequencies of the p53 codon 72 genotypes in the three groups are shown in the figure. There were no significant differences in the proportions of the different p53 codon 72 genotypes between the two control groups (screening group vs antenatal-care group, X2=3·16, df=2, p=0·21), nor between the cervical cancer group and the two control groups combined (controls vs cervical cancer group, X2=1·58, df=2, p=0·45).
Discussion
The previous study1 suggested that a subgroup of women may have a genetic susceptibility to cervical cancer, once infected by oncogenic HPV types. The results of that study suggest that about a third of UK white women would fall into the high-risk category, and therefore that reductions in cost and anxiety might be achieved by reducing the screening frequency in low-risk women. The finding of a germline genetic predisposition to cervical cancer would also have implications for the relatives of
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